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Background: We aimed to verify the validity of the proportional recovery model for the lower extremity. Methods: We reviewed clinical data of patients enrolled in the Korean Stroke Cohort for Functioning and Rehabilitation between August 2012 and May 2015. Recovery proportion was calculated as the amount of motor recovery over initial motor impairment, measured as the Fugl-Meyer Assessment of Lower Extremity score. We used the logistic regression method to model the probability of achieving the full Fugl-Meyer Assessment of Lower Extremity score, whereby we considered the ceiling effect of the score. To show the difference in the prevalence of achieving the full Fugl-Meyer Assessment of Lower Extremity score between 3 and 6 months poststroke, we constructed a marginal model through the generalized estimating equation method. We also performed the propensity score matching analysis to show the dependency of recovery proportion on the initial motor deficit at 3 and 6 months poststroke. Results: We evaluated 1085 patients. The recovery proportions at 3 and 6 months poststroke were 0.67±0.42 and 0.75±0.39, respectively. A 1-unit decrease in the initial neurological impairment and the age at stroke onset increased the probability of achieving the full Fugl-Meyer Assessment of Lower Extremity score, which occurred at both 3 and 6 months poststroke. The prevalence of those who reach full lower limb motor recovery differs significantly between 3 and 6 months poststroke. We also found out that the recovery proportion at both 3 and 6 months poststroke is determined by the initial motor deficits of the lower limb. These results are not consistent with the proportional recovery model. Conclusions: Our results demonstrated that the proportional recovery model for the lower limb is invalid.

This study was a randomized controlled trial to examine the effects of the RAPAEL® Smart Glove digital training system on upper extremity function and cortical hemodynamic changes in subacute stroke patients. Of 48 patients, 20 experimental and 16 controls completed the study. In addition to conventional occupational therapy (OT), the experimental group received game-based digital hand motor training with the RAPAEL® Smart Glove digital system, while the control group received extra OT for 30 min. The Fugl-Meyer assessment (UFMA) and Jebsen-Tayler hand function test (JTT) were assessed before (T0), immediately after (T1), and four weeks after intervention (T2). Cortical hemodynamics (oxyhemoglobin [OxyHb] concentration) were measured by functional near-infrared spectroscopy. The experimental group had significantly better improvements in UFMA (T1-T0 mean [SD]; Experimental 13.50 [7.49]; Control 8.00 [4.44]; p = 0.014) and JTT (Experimental 21.10 [20.84]; Control 5.63 [5.06]; p = 0.012). The OxyHb concentration change over the ipsilesional primary sensorimotor cortex during the affected wrist movement was greater in the experimental group (T1, Experimental 0.7943 × 10−4 μmol/L; Control −0.3269 × 10−4 μmol/L; p = 0.025). This study demonstrated a beneficial effect of game-based virtual reality training with the RAPAEL® Smart Glove digital system with conventional OT on upper extremity motor function in subacute stroke patients.

Objective To investigate long-term and serial functional outcomes in ischemic stroke patients without diabetes with post-stroke hyperglycemia.Methods The Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO) is a large, multi-center, prospective cohort study of stroke patients admitted to participating hospitals in nine areas of Korea. From KOSCO, ischemic stroke patients without diabetes were recruited and divided into two groups: patients without diabetes without (n=779) and with post-stroke hyperglycemia (n=223). Post-stroke hyperglycemia was defined as a glucose level >8 mmol/L. Functional assessments were performed 7 days and 3, 6, and 12 months after stroke onset.Results There were no significant differences in baseline characteristics between the groups, except in the age of onset and smoking. Analysis of the linear correlation between the initial National Institutes of Health Stroke Scale (NIHSS) score and glucose level showed no significant difference. Among our functional assessments, NIHSS, Fugl-Meyer Assessment (affected side), Functional Ambulatory Category, modified Rankin Scale, and Korean Mini-Mental State Examination (K-MMSE) showed statistically significant improvements in each group. All functional improvements except K-MMSE were significantly higher in patients without post-stroke hyperglycemia at 7 days and 3, 6, and 12 months.Conclusion The glucose level of ischemic stroke patients without diabetes had no significant correlation with the initial NIHSS score. The long-term effects of stress hyperglycemia showed worse functional outcomes in ischemic stroke patients without diabetes with post-stroke hyperglycemia.

ImportanceBecause stroke causes diverse functional deficits, understanding the long-term recovery pattern of each functional domain may inform prognosis and therapeutic strategies.ObjectiveTo observe long-term changes in functional status and residual disability in survivors of first-time stroke.Design, Setting, and ParticipantsThis cohort study was an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Between August 2012 and May 2015, 7858 of 10 636 screened patients with first-time strokes from 9 district hospitals in Korea provided informed consent to participate. Data were analyzed from September 2021 through February 2022.ExposureFirst-time stroke.Main Outcomes and MeasuresStudy data include multifaceted face-to-face functional assessments obtained at 8 to 9 points until 60 months after stroke onset. The Korean Mini-Mental State Examination (K-MMSE), Fugl-Meyer Assessment, Functional Ambulatory Category, American Speech-Language-Hearing Association National Outcome Measurement System Swallowing Scale, and Short Korean version of the Frenchay Aphasia Screening Test were performed from 7 days to 60 months after stroke. The Korean Modified Barthel Index was measured from 3 months to 60 months after stroke.ResultsA total of 4443 patients (2649 men [59.62%]; mean [SD] age 62.13 [12.43] years) who underwent repeated functional assessments for 60 months after stroke (3508 patients with ischemic and 935 patients with hemorrhagic stroke) were included. Overall, functions plateaued between 12 and 18 months after stroke and declined after 30 months; for example, mean (SD) K-MMSE improved from 7 days (22.89 [7.89]) to 12 months (26.03 [5.48]) (P P P for interaction P for interaction P for interaction P P = .004), and hemorrhagic stroke type (β vs ischemic stroke = 2.35; SE, 0.81; P = .004).Conclusions and RelevanceThis study found that long-term recovery patterns in multifaceted functional domains differed from one another and varied by patient age, stroke severity, and stroke type. Understanding the diversity of long-term functional recovery patterns and factors associated with these outcomes in survivors of stroke may help clinicians develop strategies for effective stroke care and rehabilitation.

This randomized controlled trial aimed to investigate the effects of dance therapy using telerehabilitation on trunk control and balance training in patients with stroke and compare them with the effects of conventional treatment.We enrolled 17 patients with subacute or chronic stroke who were randomly assigned to either an experimental or a control group. In addition to conventional physical therapy, the experimental group (n = 9) participated in 40-minute, non-face-to-face, dance-therapy sessions and the control group (n = 8) received conventional physical therapy. The primary outcome measures were the Trunk Impairment Scale (TIS) scores to assess trunk control and balance function between the 2 groups as a measure of change from baseline to after the intervention.We found that the TIS scores of the patients in the experimental group significantly improved (P = .017). The TIS results indicated non-inferiority within a predefined margin for dance therapy using telerehabilitation (difference = -0.86, 95% confidence interval [CI] = -2.21 to 0.50).Dance therapy using telerehabilitation significantly improved the TIS scores in the experimental group and was not inferior to conventional rehabilitation treatment when compared in a non-inferiority test. The remote dance program may therefore have similar effects to those of conventional treatment regarding trunk-control improvement in patients with stroke.

Background and Purpose: The therapeutic use of transcranial direct current stimulation (tDCS), an adjuvant tool for stroke, induces long-term changes in cortical excitability, for example, the secretion of activity-dependent growth factors. We assessed the proper therapeutic configuration of high-definition tDCS (HD-tDCS) in the subacute stage of ischemic stroke and its underlying expression profiling of growth factors to propose a new method for ensuring better therapeutic effects. Methods: Male C57BL/6J mice were subjected to middle cerebral artery occlusion, after which repetitive HD-tDCS (20 minutes, 55 µA/mm 2 , charge density 66 000 C/m 2 ) was applied from subacute phases of their ischemic insult. Behavioral tests assessing motor and cognitive functions were used to determine suitable conditions and HD-tDCS stimulation sites. Gene expression profiling of growth factors and their secretion and activation were analyzed to shed light on the underlying mechanisms. Results: Anodal HD-tDCS application over the contralesional cortex, especially the motor cortex, was more effective than ipsilesional stimulation in attenuating motor and cognitive deficits. In the HD-tDCS application over the contralesional motor cortex, positive changes in Bmp8b , Gdf5 , Il4 , Pdgfa , Pgf , and Vegfb were observed in the ipsilesional site. The expression of GDF5 (growth/differentiation factor 5) and PDGFA (platelet-derived growth factor subunit A) tended to similarly increase in both ipsi- and contralesional striata. However, higher expression levels of GDF5 and PDGFA and their receptors were observed in the peri-infarct regions of the striatum after HD-tDCS, especially in PDGFA expression. A higher number of proliferating or newly formed neuronal cells was detected in ipsilesional sites such as the subventricular zone. Conclusions: Application of anodal HD-tDCS over the contralesional cortex may enhance beneficial recovery through the expression of growth factors, such as GDF5 and PDGFA, in the ipsilesional site. Therefore, this therapeutic configuration may be applied in the subacute stage of ischemic stroke to ameliorate neurological impairments.

Previous studies have investigated the predictors for home discharge without considering stroke severity. To develop a practical assessment tool that predicts home discharge for moderate stroke patients after subacute rehabilitation therapy in the tertiary hospitals. Stroke patients with National Institutes of Health Stroke Scale scores of 6 to 13 were included in this prospective cohort study. Various demographic, clinical, and functional factors were analyzed as potential predictive factors. A weighted scoring model was developed through the following three-step process: 1) selection of the factors by logistic regression analyses, 2) development of a weighted scoring model, and 3) validation of the generalizability of the model. The home discharge rate was 51% (n = 372), and the overall mean length of stay of hospitalization was 32.5 days. 1) The Cognitive Functional Independence Measure, 2) the Functional Ambulation Categories, 3) the modified Charlson Comorbidity Index, and 4) marital status were independent predictors of home discharge. The coefficient value for marital status was adjusted to 1 in the scoring system, and the values of the other parameters were proportionally converted to the nearest integer. Possible total scores ranged from 0 to 13 in the model, with a higher score indicating a higher probability of home discharge. With a cutoff point of 7, this model showed 87.0% sensitivity and 86.2% specificity (area under the curve = 0.90). This novel assessment tool can be useful in predicting home discharge after subacute rehabilitation of moderate stroke patients.

Background and Purpose— The theory of cognitive reserve (CR) was introduced to account for individual differences in the clinical manifestation of neuropathology. This study investigated whether CR has a modulating effect on cognitive impairment and recovery after stroke. Methods— This study is an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. A total of 7459 patients with first-ever stroke were included for analysis. Education, occupation, and composite CR scores derived from those 2 variables were used as CR proxies. Scores from the Korean version of the Mini-Mental State Examination analyzed for 30 months after stroke onset were analyzed. Results— Lower CR increased the risk of cognitive impairment after stroke. The odds ratio was 1.89 (95% CI, 1.64–2.19) in patients with secondary education and 2.42 (95% CI, 2.03–2.90) in patients with primary education compared with patients with higher education. The odds ratio was 1.48 (95% CI, 1.23–1.98) in patients with a skilled manual occupation and 2.01 (95% CI, 1.42–2.83) in patients with a nonskilled manual occupation compared with patients with a managerial or professional occupation. In the multilevel model analysis, the Korean version of the Mini-Mental State Examination total score increased during the first 3 months (1.93 points per month) and then plateaued (0.02 point per month). The slopes were moderated by the level of education, occupation, and composite CR score: the higher the level of education, occupation, or CR score, the faster the recovery. In the older adult group, the Korean version of the Mini-Mental State Examination scores showed a long-term decline that was moderated by education level. Conclusions— Education and occupation can buffer an individual against cognitive impairment caused by stroke and promote rapid cognitive recovery early after stroke. In addition, higher education minimizes long-term cognitive decline after stroke, especially in older patients. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03402451.

One of the pathophysiologies of post-stroke spasticity (PSS) is the imbalance of the reticulospinal tract (RST) caused by injury to the corticoreticular pathway (CRP) after stroke. We investigated the relationship between injuries of the CRP and PSS using MR diffusion tensor imaging (DTI). The subjects were divided into spasticity and control groups. We measured the ipsilesional fractional anisotropy (iFA) and contralesional fractional anisotropy (cFA) values on the reticular formation (RF) of the CRP were on the DTI images. We carried out a retrospective analysis of 70 patients with ischemic stroke. The cFA values of CRP in the spasticity group were lower than those in the control group (p = 0.04). In the sub-ROI analysis of CRP, the iFA values of pontine RF were lower than the cFA values in both groups (p &lt, 0.05). The cFA values of medullary RF in the spasticity group were lower than the iFA values within groups, and also lower than the cFA values in the control group (p &lt, 0.05). This results showed the CRP injury and that imbalance of RST caused by CRP injury was associated with PSS. DTI analysis of CRP could provide imaging evidence for the pathophysiology of PSS.

Stroke in young adults has catastrophic consequences and has increased in prevalence, contrary to the trends of most other diseases. This study aimed to determine the major characteristics and risk factors for stroke in younger adults compared with older adults. From the Korean Stroke Cohort for Functioning and Rehabilitation, 10,584 patients with first-ever stroke between August 2012 and March 2015 were enrolled retrospectively and divided into younger (age ≤ 45) and older groups (age > 45). The clinical characteristics and risk factors of stroke were compared between the younger and older groups. The younger group comprised 915 patients (8.6%). The proportion of hemorrhage strokes in the younger group (42.3%) was significantly higher than in the older group (20.0%) (p < 0.001). Obesity, current smoking, and heavy alcohol consumption were significantly more common risk factors in the younger group than in the older group for all stroke types, whereas hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and coronary heart disease were significantly more frequent in the older group (both p < 0.001). The major risk factors in the younger group may be lifestyle-related. Therefore, increasing awareness of lifestyle-related risk factors may be necessary to prevent stroke in young adults.

Background and Purpose: The aim of this study was to verify the validity of the proportional recovery model in view of the ceiling effect of the Fugl-Meyer Assessment. Methods: We reviewed the medical records of patients enrolled in the Korean Stroke Cohort for Functioning and Rehabilitation between August 2012 and May 2015. Recovery proportion was defined as the actual change in Fugl-Meyer Assessment score of the upper extremity between 7 days and 6 months poststroke, relative to the initial neurological impairment. We then used logistic regression to identify clinical factors attributable to a ceiling effect of the Fugl-Meyer Assessment score of the upper extremity and propensity score matching to verify the validity of the proportional recovery rule. Results: We screened 10 636 patients and analyzed 849 patients (mean age, 65.4±11.9 years; female, 320 [37.7%]) with first-ever ischemic stroke. We found, through logistic regression analysis, that a one-unit increase in the initial neurological impairment and the age at stroke onset affected the odds ratio (1.0386 and 0.9736, respectively) of achieving the full Fugl-Meyer Assessment score of the upper limb at 6 months poststroke. We also demonstrated, through propensity score matching, that the difference in initial neurological impairment of the upper extremity resulted in discrepancy of the recovery proportion (0.92±0.20 [0–1] versus 0.81±0.31 [0–1], P Conclusions: We demonstrated that the ceiling effect of the Fugl-Meyer Assessment score of the upper extremity is pronounced in patients with mild initial motor deficits of the upper extremity and that the recovery proportion varies according to the initial motor deficit of the upper limb using logistic regression analysis and propensity score matching, respectively. These results suggest that the proportional recovery model is not valid.

The objective of this study was to evaluate whether Cerebrolysin combined with rehabilitation therapy supports additional motor recovery in stroke patients with severe motor impairment. This study analyzed the combined data from the two phase IV prospective, multicenter, randomized, double-blind, placebo-controlled trials. Stroke patients were included within seven days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo with standardized rehabilitation therapy. Assessments were performed at baseline, immediately after the treatment course, and 90 days after stroke onset. The plasticity of the motor system was assessed by diffusion tensor imaging and resting state fMRI. In total, 110 stroke patients were included for the full analysis set (Cerebrolysin n = 59, placebo n = 51). Both groups showed significant motor recovery over time. Repeated-measures analysis of varianceshowed a significant interaction between time and type of intervention as measured by the Fugl–Meyer Assessment (p &lt, 0.05). The Cerebrolysin group demonstrated less degenerative changes in the major motor-related white matter tracts over time than the placebo group. In conclusion, Cerebrolysin treatment as an add-on to a rehabilitation program is a promising pharmacologic approach that is worth considering in order to enhance motor recovery in ischemic stroke patients with severe motor impairment.

This study investigated the long-term functional changes in patients with moderate-to-severe ischemic stroke. In addition, we investigated whether there was a difference between the modified Barthel Index (MBI) and Functional Independence Measure (FIM) according to severity. To evaluate the changes in the long-term functional independence of the subjects, six evaluations were conducted over 2 years, and the evaluation was performed using MBI and FIM. A total of 798 participants participated in this study, of which 673 were classified as moderate and 125 as severe. During the first 3 months, the moderate group showed greater recovery than the severe group. The period of significant change in the National Institutes of Health Stroke Scale (NIHSS) score was up to 6 months after onset in the moderate group, and up to 3 months after onset in the severe group. In the severe group, MBI evaluation showed significant changes up to 6 months after onset, whereas FIM showed significant changes up to 18–24 months. Our results showed that functional recovery of patients with ischemic stroke in the 3 months after onset was greater in the moderate group than in the severe group. FIM is more appropriate than MBI for evaluating the functional status of patients with severe stroke.

BackgroundBrain disorders are gradually becoming the leading cause of death worldwide. However, the lack of knowledge of brain disease’s underlying mechanisms and ineffective neuropharmacological therapy have led to further exploration of optimal treatments and brain monitoring techniques.ObjectiveThis study aims to review the current state of brain disorders, which utilize transcranial electrical stimulation (tES) and daily usable noninvasive neuroimaging techniques. Furthermore, the second goal of this study is to highlight available gaps and provide a comprehensive guideline for further investigation.MethodA systematic search was conducted of the PubMed and Web of Science databases from January 2000 to October 2020 using relevant keywords. Electroencephalography (EEG) and functional near-infrared spectroscopy were selected as noninvasive neuroimaging modalities. Nine brain disorders were investigated in this study, including Alzheimer’s disease, depression, autism spectrum disorder, attention-deficit hyperactivity disorder, epilepsy, Parkinson’s disease, stroke, schizophrenia, and traumatic brain injury.ResultsSixty-seven studies (1,385 participants) were included for quantitative analysis. Most of the articles (82.6%) employed transcranial direct current stimulation as an intervention method with modulation parameters of 1 mA intensity (47.2%) for 16–20 min (69.0%) duration of stimulation in a single session (36.8%). The frontal cortex (46.4%) and the cerebral cortex (47.8%) were used as a neuroimaging modality, with the power spectrum (45.7%) commonly extracted as a quantitative EEG feature.ConclusionAn appropriate stimulation protocol applying tES as a therapy could be an effective treatment for cognitive and neurological brain disorders. However, the optimal tES criteria have not been defined; they vary across persons and disease types. Therefore, future work needs to investigate a closed-loop tES with monitoring by neuroimaging techniques to achieve personalized therapy for brain disorders.

Background: This study investigated the impact of post-stroke depression (PSD) on cognitive aging in elderly stroke patients. Methods: This study was an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Among 10,636 patients with first-ever stroke, a total of 3215 patients with normal cognitive function three months post-stroke were included in the analysis. PSD was defined using the Korean Geriatric Depression Scale Short Form (K-GDS-SF) at three months. Cognitive aging was defined as a decline in the Korean version of the Mini-Mental Status Examination (K-MMSE) score to less than the second percentile. Results: The hazard ratio (HR) of PSD for cognitive decline was 2.16 (95% CI, 1.34–3.50, p < 0.01) in the older group (age ≥65 years), and 1.02 (95% CI, 0.50–2.07, n.s.) in the younger group (age

Objective The aim of the study was to analyze differences in body composition between affected and unaffected limbs using segmental bioelectrical impedance analysis in hemiparetic stroke patients. Design The segmental bioelectrical impedance analysis results and body composition of 213 hospitalized hemiparetic stroke patients were retrospectively reviewed. Subjects were divided into acute, subacute, and chronic groups according to the period after the onset of stroke. Segmental lean mass and segmental body water values were compared between affected and unaffected upper and lower limbs in all subjects and in subgroups. The mean differences of body compositions between the affected and unaffected limbs between the three groups were also compared. Results No significant differences in segmental lean mass and segmental body water values were observed between the affected and unaffected upper and lower limbs in total and in three subgroups. The mean differences in segmental lean mass and segmental body water values between the affected and unaffected upper limbs in the chronic group were larger than those in the acute and subacute groups. Conclusions There were no significant differences in body composition between affected and unaffected limbs in patients with hemiparetic stroke. The differences in body composition in the affected and unaffected upper limbs in chronic stroke patients were larger than those in acute and subacute stroke patients. Further longitudinal studies are needed.

Although over one-third of stroke patients may develop post-stroke cognitive impairment (PSCI), the mechanisms underlying PSCI remain unclear. We explored here, the involvement of post-stroke inflammasomes in long-term PSCI development, using a 45 min-middle cerebral artery occlusion (MCAO)/reperfusion-induced PSCI model. Immunohistological assessment on day 1, 3, and 7 was followed by cognitive function test 28 days post-stroke. Evaluation of inflammasome sensor gene expression in aged mouse brains showed dominant expression of absent in melanoma 2 (Aim2) in 6-, 12-, and 18-month-old mouse brains. AIM2 mRNA and protein increased until 7 days post-stroke. PSCI decreased anxiety in elevated plus maze test and impaired spatial learning and memory functions in Morris water maze test 28 days post-stroke. AIM2 and other inflammasome subunit immunoreactivities, including those for caspase-1, interleukin (IL)-1β, and IL-18, were higher in the hippocampus and cortex of the PSCI than in those of the sham group 7 days post-stroke. AIM2 immunoreactivity of the PSCI group was primarily co-localized with Iba-1 (microglial marker) and CD31 (endothelial cell marker) immunoreactivities but not NeuN (neuronal marker) and GFAP (astrocyte marker) immunoreactivities, suggesting that microglia or endothelial cell-induced AIM2 production mediated PSCI pathogenesis. Additionally, inflammasome-induced pyroptosis might contribute to acute and chronic neuronal death after stroke. AIM2 knockout (KO) and Ac-YVAD-CMK-induced caspase-1 inhibition in mice significantly improved cognitive function and reversed brain volume in the hippocampus relative to those in stroke mice. Conclusively, AIM2 inflammasome-mediated inflammation and pyroptosis likely aggravated PSCI; therefore, targeting and controlling AIM2 inflammasome could potentially treat PSCI.

The aim of the study was to investigate the correlation between spasticity severity and functional outcomes during the first year after stroke.The Korean Stroke Cohort for Functioning and Rehabilitation is a large, multicenter, prospective cohort study of all patients with acute first-ever stroke admitted to participating hospitals in nine Korean areas. To investigate the correlation between spasticity severity and functional status measured by using the Institutes of Health Stroke Scale (NIHSS), Modified Barthel Index (MBI), Functional Independence Measurement (FIM), Fugl-Meyer Assessment (FMA), Functional Ambulatory Category (FAC), modified Rankin scale (mRS), and American Speech-Language Hearing Association National Outcome Measurement System Swallowing Scale (ASHA-NOMS), data were analyzed at 3, 6, and 12 mos after the occurrence of stroke.A total of 7359 stroke patients, 3056 were finally included. Prevalence rates of spasticity in patients after stroke were 6.8% at 3 mos, 6.9% at 6 mos, and 7.6% at 12 mos. The scores of mRS and NIHSS were higher and those of K-MBI, FIM, FMA, and ASHA-NOMS were lower in more severe spastic patients, indicating poorer functional outcomes (P0.05).This study demonstrated the coexistence of spasticity and poor functional outcome during the first year after first-ever stroke patients.

We prepared and grafted tropomyosin receptor kinase B (TrkB) gene-transfected mesenchymal stem cells (TrkB-MSCs) into the ischemic penumbra and investigated whether electroacupuncture (EA) treatment could promote functional recovery from ischemic stroke. For the behavioral test, TrkB-MSCs+EA resulted in significantly improved motor function compared to that obtained with MSCs+EA or TrkB-MSCs alone. At 30 days after middle cerebral artery occlusion (MCAO), the largest number of grafted MSCs was detected in the TrkB-MSC+EA group. Some differentiation into immature neuroblasts and astrocytes was detected; however, only a few mature neuron-like cells were found. Compared to other treatments, TrkB-MSCs+EA upregulated the expression of mature brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT4) and induced the activation of TrkB receptor and its transcription factor cAMP response element-binding protein (CREB). At 60 days after MCAO, EA highly promoted the differentiation of TrkB-MSCs into mature neuron-like cells compared to the effect in MSCs. A selective TrkB antagonist, ANA-12, reverted the effect of TrkB-MSCs+EA in motor function recovery and survival of grafted MSCs. Our results suggest that EA combined with grafted TrkB-MSCs promotes the expression of BDNF and NT4, induces the differentiation of TrkB-MSCs, and improves motor function. TrkB-MSCs could serve as effective therapeutic agents for ischemic stroke if used in combination with BDNF/NT4-inducing therapeutic approaches.

Objective To identify contributing factors that can be used to predict which patients with first-ever stroke will return to driving during 1 year after stroke. Design Multicentre cohort study. Subjects A total of 620 first-ever stroke patients who drove before stroke. Methods The Stroke Cohort for Functioning and Rehabilitation is a large, multicentre, prospective cohort study of all patients with acute first-ever stroke admitted to participating hospitals in 9 areas of Korea. This study analysed the data from 1,354 patients who completed a face-to-face survey about return to driving at 1 year after stroke. A multiple binary logistic regression analysis model was used to analyse factors that potentially influenced return to driving during 12 months after stroke. Results Of 620 subjects, 410 (66.1%) returned to driving after stroke. They resumed driving at a mean of 2.15 months after stroke (standard deviation 2.32 years). Regression models showed that sex, age, modified Rankin scale (mRS), education about return to driving, and Fugl-Meyer Assessment (FMA) were significantly related to return to driving. Stroke type, ambulatory function, and language function at 7 days were not correlated with return to driving. Conclusion Male patients, education about return to driving, lower mRS, and higher FMA at 7 days after stroke are predictors of return to driving. This model could be used by clinicians to help counsel patients and their families.

Objective To identify the incidence of dysphagia after ischemic stroke and determine factors affecting the presence of dysphagia. Design Retrospective case-control study. This was an interim analysis of a prospective multicenter Korean stroke cohort. Setting Acute care university hospitals. Participants Patients (N=6000) with first-ever acute ischemic stroke. Patients were divided into 2 groups according to the presence or absence of dysphagia confirmed at 7 days after onset using the American Speech-Language-Hearing Association National Outcomes Measurement System (ASHA-NOMS) scale, which was determined after conducting screening or standardized tests. Interventions Not applicable. Main Outcome Measures Age at stroke onset, body mass index (BMI), premorbid modified Rankin Scale (mRS), brainstem lesions, National Institutes of Health Stroke Scale (NIHSS), poststroke mRS, and ASHA-NOMS swallowing level at poststroke day 7 were evaluated. Results Among patients with ischemic stroke, 32.3% (n=1940) had dysphagia at 7 days after stroke onset. At discharge, 80.5% (n=1561) still had dysphagia. The prediction model for the presence of dysphagia identified age at onset, underweight (BMI Conclusions The incidence of dysphagia after ischemic stroke was 32.3%. The prediction model for the presence of dysphagia identified age, low BMI, premorbid disabilities, brainstem lesions, and NIHSS as predictive factors.

We aimed to investigate the effects of low-level light emitting diode therapy (LED-T) on the long-term functional outcomes after cerebral ischemia, and the optimal timing of LED-T initiation for achieving suitable functional recovery. Focal cerebral ischemia was induced in mice via photothrombosis. These mice were assigned to a sham-operated (control), ischemic (vehicle), or LED-T group [initiation immediately (acute), 4 days (subacute) or 10 days (delayed) after ischemia, followed by once-daily treatment for 7 days]. Behavioral outcomes were assessed 21 and 28 days post-ischemia, and histopathological analysis was performed 28 days post-ischemia. The acute and subacute LED-T groups showed a significant improvement in motor function up to 28 days post-ischemia, although no brain atrophy recovery was noted. We observed proliferating cells (BrdU+) in the ischemic brain, and significant increases in BrdU+/GFAP+, BrdU+/DCX+, BrdU+/NeuN+, and CD31+ cells in the subacute LED-T group. However, the BrdU+/Iba-1+ cell count was reduced in the subacute LED-T group. Furthermore, the brain-derived neurotrophic factor (BDNF) was significantly upregulated in the subacute LED-T group. We concluded that LED-T administered during the subacute stage had a positive impact on the long-term functional outcome, probably via neuron and astrocyte proliferation, blood vessel reconstruction, and increased BDNF expression. Picture: The rotarod test for motor coordination showed that acute and subacute LED-T improves long-term functional recovery after cerebral ischemia.

BACKGROUND Noninvasive brain stimulation (NBS) using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has recently been adopted for modulating motor function in stroke patients. OBJECTIVE We investigated the effect of simultaneous dual-mode stimulation using rTMS and tDCS over the bilateral primary motor cortices (M1) to assess its efficacy as compared to single stimulation using rTMS for the recovery of motor function in subacute stroke patients. METHODS Thirty subacute stroke patients were recruited in this study. In the dual-mode stimulation group, 10 Hz rTMS (90% of resting motor threshold, 1,000 pulses) was applied over the ipsilesional M1 for 20 minutes with the simultaneous application of cathodal tDCS (2 mA) on the contralesional M1. The single stimulation group underwent 10 Hz rTMS without tDCS. Ten daily sessions were conducted for two consecutive weeks. The total Fugl-Meyer (FMA-T), upper limb (FMA-UL), and lower limb (FMA-LL) scores were measured before, after, and two months later. RESULTS The FMA-T and FMA- UL were significantly improved over time in both the dual and single stimulation group (p

Objective To investigate whether bihemispheric anodal transcranial direct current stimulation (tDCS) with conventional dysphagia therapy could improve swallowing function in chronic stroke patients with dysphagia. Design Randomized controlled trial. Subjects Twenty-six patients with dysphagia for at least 6 months post-stroke were randomly assigned into: (i) bihemispheric anodal tDCS group; or (ii) sham group. Methods All patients underwent 10 tDCS sessions with simultaneous conventional swallowing therapy for 2 weeks. Both anodal electrodes were attached bilaterally to the pharyngeal motor cortices, and cathodal electrodes were attached to both supraorbital regions. Swallowing function was evaluated with the Dysphagia Outcome and Severity Scale (DOSS) before and immediately after the last intervention session. Results The bihemispheric anodal tDCS group showed a mean significant improvement 0.62 points; standard deviation (SD) 0.77, in the DOSS immediately after all sessions (p = 0.02). However, there was no mean significant improvement in the sham group (0.38 points; SD 0.65(p = 0.06)). There was no significant difference between the 2 groups (p = 0.48). Conclusion The bihemispheric anodal tDCS with conventional dysphagia therapy had additional helpful effects on the improvement in swallowing function in chronic stroke patients.

Objective: The objective of this study was to apply the clustering approach of multi-facet functional recovery pattern with big data of in the Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO) using artificial intelligence, and to provide valuable prediction models for clinically use. Methods: This study was an interim analysis of the KOSCO designed as 10 years long-term follow-up study of stroke patients. We analyzed data of participants who completed functional assessments from 7 days to 12 months after ischemic stroke onset. Functional assessments included Korean modified Barthel Index (K-MBI), Korean Mini-Mental State Examination (K-MMSE), Fugl-Meyer Assessment (FMA), Functional Ambulatory Category (FAC), the American Speech-Language-Hearing Association National Outcome Measurement System Swallowing Scale (ASHA-NOMS), and Short Korean Version of Frenchay Aphasia Screening Test (Short K-FAST). The cluster analysis using artificial intelligence was performed for multi-facet functional recovery patterns of independency, motor, ambulation, cognition, language, and swallowing functions. After the cluster analysis, a group of rehabilitation specialists reviewed the clinical meaningfulness with clustered population, whether the groups had high homogeneity and representativeness of the clinical stroke recovery patterns. After these clustering approaches, a prediction model using machine learning was performed. The accuracy of classification of this prediction model was evaluated by comparing how much the prediction was equivalent to the actual clustering result. Results: After the machine learning in supervised manners on artificial intelligence, recovery patterns after stroke could be classified into ten groups. Each group showed a different multi-facet functional recovery pattern from 7 day to 12 months, and this clustering showed a clinically acceptance. In addition, the accuracy in classification with clinical characteristics at 7 days showed more than 73.0%. Conclusion: The results of this study demonstrated the potentials of the clustering and predicting functional recovery patterns of stroke patients using artificial intelligence.

Objective: The objective of this study was to investigate differences of functional recovery pattern and the factors associated with recovery pattern between male and female stroke patients. Methods: This study was an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO) designed as 10 years long-term follow-up study of stroke patients. We analyzed serial data up to 24 months of multi-facet functional assessments such as Korean-Modified Barthel Index (K-MBI), Fugl-Meyer Assessment (FMA), Functional ambulation classification (FAC), American Speech-Language-Hearing Association-National Outcomes Measurement System (ASHA-NOMS), Korean version of Frenchay Aphasia Screening Test (K-FAST) to identify sex-specific differences after adjustments for difference with age, type of stroke, premorbid functional level, degree of comorbidity, and multi-facet functional levels at 7 day after stroke. Results: Out of total 10,636 stroke patients (6,043 male and 4,593 female), female patients showed significantly older age, lower education level, lower body mass index, worse premorbid functional level, higher co-morbidity and more severe initial severity assessed by NIHSS compared with male stroke patients (p Conclusion: The results of this study could provide more specific information for establishing the stroke rehabilitation strategy according to sex.

OBJECTIVE To evaluate the efficacy of intra-articular hyaluronic acid (IAHA) injection for hemiplegic shoulder pain (HSP) after stroke. METHODS Thirty-one patients with HSP and limited range of motion (ROM) without spasticity of upper extremity were recruited. All subjects were randomly allocated to group A (n=15) for three weekly IAHA injection or group B (n=16) for a single intra-articular steroid (IAS) injection. All injections were administered by an expert physician until the 8th week using a posterior ultrasonography-guided approach. Shoulder joint pain was measured using the Wong-Baker Scale (WBS), while passive ROM was measured in the supine position by an expert physician. RESULTS There were no significant intergroup differences in WBS or ROM at the 8th week. Improvements in forward flexion and external rotation were observed from the 4th week in the IAHA group and the 8th week in the IAS group. Subjects experienced a statistically significant improvement in pain from the 1st week in the IAS and from the 8th week in IAHA group, respectively. CONCLUSION IAHA seems to have a less potent ability to reduce movement pain compared to steroid in the early period. However, there was no statistically significant intergroup difference in WBS and ROM improvements at the 8th week. IAHA might be a good alternative to steroid for managing HSP when the use of steroid is limited.

BACKGROUND AND PURPOSE High-frequency repetitive transcranial magnetic stimulation (rTMS) aids motor recovery in patients with subacute stroke. However, the response to high-frequency rTMS is highly variable between patients. The aim of this study was to identify the factors associated with improved motor function in response to high-frequency rTMS in subacute stroke patients with moderate to severe upper extremity motor involvement. METHODS Sixty-two patients with subacute stroke were enrolled. rTMS was applied over the primary motor cortex of the affected hemisphere at 10 Hz with 1,000 pulses/day for 10 days. Upper limb motor function was scored with the upper limb of Fugl-Meyer Assessment (FMA-UL) score before intervention and immediately after intervention. All FMA-UL changes greater than or equal to 5 points were considered clinically significant. Potential influencing factors considered included patient characteristics, motor function, corticospinal tract (CST) integrity assessments, and genetics. Multivariate logistic regression analysis was used to identify the significance of each of these factors. RESULTS We found that the two factors with the greatest impact on the improvement in FMA-UL score were: 1) the functional integrity of the CST, and 2) the brain-derived neurotrophic factor (BDNF) genotype (p

Background There are a few reports on the impact of central facial palsy and dysarthria on quality of life (QOL) in stroke patients. Objective To investigate the impact of central facial palsy on QOL compared with dysarthria during the chronic phase in patients with first-ever strokes. Methods This study represents an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation study. We selected data from patients with functional independence of 0 or 1 by the modified Rankin Scale at 6 months after stroke onset, who showed an impairment only in National Institute of Health Stroke Scale items 4 (facial palsy) or 10 (dysarthria). Assessments included the European Quality of Life-5 Dimensions (EQ-5D) and the Geriatric depression scale-short form (GDS-SF). Results Data from 149 patients were selected for this analysis from 3,929 patients who were followed up at 6 months. Thirty-nine and 110 patients were classified into the facial palsy and dysarthria groups, respectively. The groups did not differ significantly in baseline characteristics or functional assessments. EQ-5D was significantly lower in the facial palsy group than in the dysarthria group at 6 months after stroke (p = 0.036). GDS-SF was significantly higher in the facial palsy group than in the dysarthria group (p = 0.005). Conclusions The results of this study revealed that central facial palsy clearly has a more negative impact on QOL than dysarthria in chronic stroke patients with functional independence.

Purpose The aim of this study was to assess the proper timing of extradural cortical stimulation (ECS) on the motor relearning in a rat model of subacute photothrombotic stroke. Methods Photothrombotic infarction was induced on the dominant sensorimotor cortex in male Sprague-Dawley rats after training in a single-pellet reaching task (SPRT). Rats were randomly divided into three groups after stroke: ECS during the inactive period (Day-ECS group), ECS during the active period (Night-ECS group) and no ECS (Non-stimulated group). Six sham-operated rats were assigned to the control group. The Day- and Night-ECS group received continuous ECS for 12 hours during the day or night for 2 weeks from day 4 after the stroke. Behavioral assessment with SPRT was performed daily. Results SPRT showed a significantly faster and greater improvement in the Day and Night-ECS groups than in the Non-stimulated group. In the Day- and Night-ECS groups, the success rate of SPRT differed significantly from Non-stimulated group on day 11 and day 8, respectively. In addition, the Night-ECS group showed a significantly higher SPRT success rate than the Day-ECS group from days 10 to 13. Conclusion ECS during the active period might be more effective for motor relearning in the subacute stroke rat model.

Predicting functional outcome and quality of life (QOL) is critical to the treatment of patients with stroke. The purpose of this study was to analyze the factors influencing functional status and QOL of stroke patients 6 months after a first-ever stroke. This study was an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation Study, designed to include 10 years of follow-up for first-ever stroke patients. This study analyzed data from 2857 patients who completed face-to-face assessments with the functional independence measurement (FIM) and Euro Quality of Life-5D (EQ-5D) at 6 months after stroke onset. A multivariate regression analysis was used to analyze factors that potentially influenced FIM and EQ-5D results at 6 months after stroke. Of the patients in this study, 80.1 % suffered from ischemic stroke and 19.9 % experienced hemorrhagic stroke. The independent predictors of functional independency measured by FIM at 6 months after stroke were age, initial stroke severity, duration of hospitalization, and functional level at discharge in terms of motor, ambulation, and language. For QOL measured by EQ-5D at 6 months after stroke, age, duration of hospitalization, and motor function at discharge were significant predictors. In conclusion, proper treatment to achieve maximal functional gain at discharge may be an important factor in improving functional independency and QOL in chronic stage stroke survivors. These results provide useful information for establishing comprehensive and systematic care for stroke patients.

Objective To investigate the return to work status of patients with first-ever stroke with functional independence 6 months post-stroke. Design Prospective cohort study. Participants Nine hundred and thirty-three patients with functional independence at 6 months after stroke onset. Methods A complete post-enumeration survey was performed through a review of the medical records for first admission. In addition, structured self-administered questionnaires and a face-to-face interview were performed assessing occupational status, quality of life, and emotional status at 6 months after stroke. Results Of the patients in this study, 60.0% returned to work at 6 months after stroke. Sex, age, educational level, and comorbidity level were independent factors related to return to work. The rate of return to work in female patients under 65 years of age was similar to that of male patients 65 years of age or older. Stroke patients who returned to work showed better emotional statuses than those who did not return to work. Conclusion Many stroke patients did not return to work despite functional independence at 6 months after stroke. Based on the results of this study, we suggest providing appropriate vocational rehabilitation for stroke patients and proper education for employers to increase the rate of early return to work in stroke patients.

Assessment of functional independence and residual disability is very important for measuring treatment outcome after stroke. The modified Rankin Scale (mRS) and the modified Barthel Index (MBI) are commonly used scales to measure disability or dependence in activities of daily living (ADL) of stroke survivors. Lack of consensus regarding MBI score categories has caused confusion in interpreting stroke outcomes. The purpose of this study was to identify the optimal corresponding MBI and modified Rankin scale (mRS) grades for categorization of MBI. The Korean versions of the MBI (K-MBI) and mRS were collected from 5,759 stroke patients at 3 months after onset of stroke. The sensitivity and specificity were calculated at K-MBI score cutoffs for each mRS grade to obtain optimally corresponding K-MBI scores and mRS grades. We also plotted receiver operating characteristic (ROC) curves of sensitivity and specificity and determined the area under the curve (AUC). The K-MBI cutoff points with the highest sum of sensitivity and specificity were 100 (sensitivity 0.940; specificity 0.612), 98 (sensitivity 0.904; specificity 0.838), 94 (sensitivity 0.885; specificity 0.937), 78 (sensitivity 0.946; specificity, 0.973), and 55 (sensitivity 937; specificity 0.986) for mRS grades 0, 1, 2, 3, and 4, respectively. From this result, the K-MBI cutoff score range for each mRS grade can be obtained. For mRS grade 0, the K-MBI cutoff score is 100, indicating no associated score range. For mRS grades 1, 2, 3, 4, and 5, the K-MBI score ranges is from 99 to 98, 97 to 94, 93 to 78, 77 to 55, and under 54, respectively.The AUC for the ROC curve was 0.791 for mRS grade 0, 0.919 for mRS grade 1, 0.970 for mRS grade 2, 0.0 for mRS grade 3, and 0.991 for mRS grade 4. The K-MBI cutoff score ranges for representing mRS grades were variable; mRS grades 0, 1, and 2 had narrow K-MBI score ranges, while mRS grades 3, 4, and 5 exhibited broad K-MBI score ranges. mRS grade seemed to sensitively differentiate mild residual disability of stroke survivors, whereas K-MBI provided more specific information of the functional status of stroke survivors with moderate to severe residual impairment.

The aim of the study was to compare the effects of progressive reducing assistance force versus full assistance force controlled robot-assisted gait training combined with conventional physiotherapy on locomotor functions in patients with subacute stroke.Inpatients with subacute stroke (N = 29; 16 men; Functional Ambulation Category score = 1 ± 0.9) were randomly assigned to one of two groups: a progressive reducing assistance force group (n = 15) or a full assistance force group (n = 14). The progressive reducing assistance force group performed robot-assisted gait training sessions from 100% assistance force at the outset to 60% assistance force at the end of the robot-assisted gait training, whereas the full assistance force group received 100% assistance force throughout the robot-assisted gait training sessions. Both groups performed robot-assisted gait training combined with conventional physiotherapy 5 days a week for 4 wks. After intervention, all patients then underwent only conventional physiotherapy 5 days a week for 4 wks of follow-up.The Mann-Whitney U test between-group comparisons showed that improvements were significantly greater in the progressive reducing assistance force group for the Functional Ambulation Category, knee extensors torque, and Berg Balance Scale relative to the full assistance force group, both at postintervention and at follow-up.Progressive reducing assistance force control during robot-assisted gait training combined with conventional physiotherapy may be more beneficial for improving locomotor functions in patients with subacute stroke.

Aim. Poststroke depression (PSD), which occurs in approximately one-third of stroke survivors, is clinically important because of its association with slow functional recovery and increased mortality. In addition, the underlying pathophysiological mechanisms are still poorly understood. Methods. We used a mouse model of PSD to examine the neurobiological mechanisms of PSD and the beneficial effects of aripiprazole, an atypical antipsychotic drug. PSD was induced in mice by combining middle cerebral artery occlusion (MCAO) with spatial restraint stress. The body weight, sucrose preference, and forced swim tests were performed at 5, 7, and 9 weeks and the Morris water maze test at 10 weeks after completing MCAO and spatial restraint stress. Results. Mice subjected to MCAO and spatial restraint stress showed significant depressive-like behavior in the sucrose preference test and forced swim test as well as cognitive impairment in the Morris water maze test. The PSD-like phenotype was accompanied by an indoleamine 2,3-dioxygenase 1 (IDO1) expression increase in the nucleus accumbens, hippocampus, and hypothalamus, but not in the striatum. Furthermore, the increased IDO1 levels were localized in Iba-1(+) cells but not in NeuN(+) or GFAP(+) cells, indicating that microglia-induced IDO1 expression was prominent in the PSD mouse brain. Moreover, 3-hydroxyanthranilate 3,4-dioxygenase (HAAO), quinolinic acid (QUIN), and reactive oxygen species (ROS) were significantly increased in the nucleus accumbens, hippocampus, and hypothalamus of PSD mice. Importantly, a 2-week aripiprazole (1 mg/kg, per os) regimen, which was initiated 1 day after MCAO, ameliorated depressive-like behavior and impairment of cognitive functions in PSD mice that was accompanied by downregulation of IDO1, HAAO, QUIN, and ROS. Conclusions. Our results suggest that the IDO1-dependent neurotoxic kynurenine metabolism induced by microglia functions in PSD pathogenesis. The beneficial effect of aripiprazole on depressive-like behavior and cognitive impairment may be mediated by inhibition of IDO1, HAAO, QUIN, and ROS.

Background and Purpose Few studies have investigated the relationship between the specific functional factors potentially associated with functional level and stroke recurrence. We conducted a study of patients with noncardioembolic ischemic stroke (NCIS) to determine the functional factors affecting recurrence within the first year. Methods In total, 568 first-ever NCIS patients (age=65.1±17.4 years, mean±SD) were analyzed in a multicenter, prospective cohort study registered from August 2012. Demographic characteristics, past medical history, comorbidities, laboratory data, stroke features in neuroimaging, acute treatments, and medications at discharge were assessed. Functional factors reflecting gross functional impairment, ambulatory function, motor function, activities of daily living, cognition, language ability, swallowing function, mood, and quality of life were comprehensively evaluated in face-to-face assessments using standardized tools at the time of discharge. Results The cumulative incidence of stroke recurrence in NCIS was 6.0% (n=34) at 1 year. The period from admission to discharge was 34.4±7.0 days. The independent predictors of stroke recurrence within 1 year in multivariate Cox proportional-hazards regression analyses were 1) age [per-year hazard ratio (HR)=1.04, 95% confidence interval (CI)=0.97–1.06, p=0.048], 2) Charlson Comorbidity Index higher than 2 (HR=1.72, 95% CI=1.26–2.22, p=0.016), 3) modified Rankin Scale score of 3 or more at discharge (HR=1.56, 95% CI=1.22–1.94, p=0.032), and 4) Functional Ambulation Category of 3 or less at discharge (HR=2.56, 95% CI=1.84–3.31, p=0.008). Conclusions In addition to patient age, moderate-to-severe functional impairment requiring the help of others (especially for ambulation) at the time of discharge and the severity of comorbidity were independent predictors of stroke recurrence within 1 year of the first NCIS.

Background Robotic-assisted gait training (RAGT) has been proposed as a novel, promising intervention paradigm to improve gait function in subacute or chronic stroke neurorehabilitation. However, the benefits of RAGT combined with conventional physical therapy for gait recovery in patients with subacute and chronic hemiparetic stroke remain unclear. Objectives The aim of the present study was to compare the effect of RAGT combine with conventional physical therapy on hip joint kinetics, kinematics, and clinical function characteristics between subacute and chronic hemiparetic stroke. Methods Seventeen patients with hemiparetic stroke (nine subacute and eight chronic patients) performed progressive RAGT (session 1, 40 min) combined with conventional physical therapy (session 1, 40 min) 5 days per week, for an average of 86 sessions over 8 weeks. The clinical outcomes included the Functional Ambulation Category (FAC), modified Rankin scale (mRS), Korean version of the modified Barthel index (K-MBI), and modified Ashworth scale, in addition to hip joint kinetics and kinematics before and after intervention. Results The mean change in active torque, resistive torque, and stiffness in the paretic hip joint did not differ significantly between the two groups. However, Cohen's effect size suggested a moderate difference between the groups in the hip flexion phase (d = 0.58, d = 0.70, and d = 0.70). The mean change in maximal hip flexion kinematics in the chronic group was significantly greater than that in the subacute group (p = 0.04, d = -0.70). The mean change in the clinical function test results between the groups was not statistically significant. However, both groups showed significantly improved FAC, mRS, and K-MBI scores. Conclusions RAGT combine with conventional physical therapy may be useful when selecting therapeutic interventions to improve the active torque, resistive torque, and stiffness in the paretic hip flexion phase in patients with chronic hemiparetic stroke who reached a plateau in the maximum locomotor recovery after conventional locomotor training.