Randomized, multicenter, comparative study of NEURO versus CIMT in poststroke patients with upper limb hemiparesis: the NEURO-VERIFY Study.

BACKGROUND: Many poststroke patients suffer functional motor limitation of the affected upper limb, which is associated with diminished health-related quality of life. AIMS: The aim of this study is to conduct a randomized, multicenter, comparative study of low-frequency repetitive transcranial magnetic stimulation combined with intensive occupational therapy, NEURO (NovEl intervention Using Repetitive TMS and intensive Occupational therapy) versus constraint-induced movement therapy in poststroke patients with upper limb hemiparesis. METHODS: In this randomized controlled study of NEURO and constraint-induced movement therapy, 66 poststroke patients with upper limb hemiparesis were randomly assigned at 2:1 ratio to low-frequency repetitive transcranial magnetic stimulation plus occupational therapy (NEURO group) or constraint-induced movement therapy (constraint-induced movement therapy group) for 15 days. Fugl-Meyer Assessment and Wolf Motor Function Test and Functional Ability Score of Wolf Motor Function Test were used for assessment. RESULTS: No differences in patients' characteristics were found between the two groups at baseline. The Fugl-Meyer Assessment score was significantly higher in both groups after the 15-day treatment compared with the baseline. Changes in Fugl-Meyer Assessment scores and Functional Ability Score of Wolf Motor Function Test were significantly higher in the NEURO group than in the constraint-induced movement therapy group, whereas the decrease in the Wolf Motor Function Test log performance time was comparable between the two groups (changes in Fugl-Meyer Assessment score, NEURO: 5·39 ± 4·28, constraint-induced movement therapy: 3·09 ± 4·50 points; mean ± standard error of the mean; P < 0·05) (changes in Functional Ability Score of Wolf Motor Function Test, NEURO: 3·98 ± 2·99, constraint-induced movement therapy: 2·09 ± 2·96 points; P < 0·05). CONCLUSIONS: The results of the 15-day rehabilitative protocol showed the superiority of NEURO relative to constraint-induced movement therapy; NEURO improved the motion of the whole upper limb and resulted in functional improvement in activities of daily living.

A multi-center study on low-frequency rTMS combined with intensive occupational therapy for upper limb hemiparesis in post-stroke patients.

BACKGROUND: Both low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) have been recently reported to be clinically beneficial for post-stroke patients with upper limb hemiparesis. Based on these reports, we developed an inpatient combination protocol of these two modalities for the treatment of such patients. The aims of this pilot study were to confirm the safety and feasibility of the protocol in a large number of patients from different institutions, and identify predictors of the clinical response to the treatment. METHODS: The study subjects were 204 post-stroke patients with upper limb hemiparesis (mean age at admission 58.5 ± 13.4 years, mean time after stroke 5.0 ± 4.5 years, ± SD) from five institutions in Japan. During 15-day hospitalization, each patient received 22 treatment sessions of 20-min low-frequency rTMS and 120-min intensive OT daily. Low-frequency rTMS of 1 Hz was applied to the contralesional hemisphere over the primary motor area. The intensive OT, consisting of 60-min one-to-one training and 60-min self-exercise, was provided after the application of low-frequency rTMS. Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were performed serially. The physiatrists and occupational therapists involved in this study received training prior to the study to standardize the therapeutic protocol. RESULTS: All patients completed the protocol without any adverse effects. The FMA score increased and WMFT log performance time decreased significantly at discharge, relative to the respective values at admission (change in FMA score: median at admission, 47 points; median at discharge, 51 points; p < 0.001. change in WMFT log performance time: median at admission, 3.23; median at discharge, 2.51; p < 0.001). These changes were persistently seen up to 4 weeks after discharge in 79 patients. Linear regression analysis found no significant relationship between baseline parameters and indexes of improvement in motor function. CONCLUSIONS: The 15-day inpatient rTMS plus OT protocol is a safe, feasible, and clinically useful neurorehabilitative intervention for post-stroke patients with upper limb hemiparesis. The response to the treatment was not influenced by age or time after stroke onset. The efficacy of the intervention should be confirmed in a randomized controlled study including a control group.

Application of combined 6-Hz primed low-frequency rTMS and intensive occupational therapy for upper limb hemiparesis after stroke.

INTRODUCTION: The purpose of this study was to clarify the safety, feasibility and efficacy of 6-Hz primed low-frequency repetitive transcranial magnetic stimulation (rTMS) applied with intensive occupational therapy (OT) for upper limb hemiparesis after stroke. SUBJECTS AND METHODS: Eleven patients with history of stroke and upper limb hemiparesis (age at intervention: 61.0 ± 13.7 years, time after stroke onset: 70.2 ± 39.8 months) were studied. Each patient received 22 sessions of 6-Hz primed low-frequency rTMS (10-min 6-Hz priming stimulation followed by 20-min low-frequency rTMS of 1-Hz) applied to the non-lesional hemisphere plus intensive OT comprising 60-min one-to-one training and 60-min self-training during 15-day hospitalization. The motor function of the affected upper limb was evaluated by Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) on the days of admission and discharge. RESULTS: All patients completed the 15-day protocol without any adverse effects. The treatment increased the FMA score (from 42.2 ± 6.9 to 45.6 ± 7.2 points, p< 0.005) and shortened the log performance time of WMFT (from 3.26 ± 1.21 to 2.81 ± 1.26 sec, p< 0.05). CONCLUSIONS: The 15-day protocol of 6-Hz primed low-frequency rTMS combined with intensive OT seems safe and a potentially useful therapeutic modality for upper limb hemiparesis after stroke.

Baseline severity of upper limb hemiparesis influences the outcome of low-frequency rTMS combined with intensive occupational therapy in patients who have had a stroke.

OBJECTIVE: To clarify whether the efficacy of combined low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) depends on baseline severity of upper limb hemiparesis after stroke. DESIGN: Retrospective comparative study. SETTING: Department of Rehabilitation Medicine at a university hospital. SUBJECTS: Fifty-two patients who had sustained a stroke and had upper limb hemiparesis (age: 57 ± 13 years; time after onset: 50 ± 33 months). Based on the Brunnstrom stage for hand-fingers at admission, patients were divided into a Stage 3 group (n = 13), a Stage 4 group (n = 20), and a Stage 5 group (n = 19). INTERVENTIONS: During a 15-day hospitalization, each patient underwent 22 sessions of 20-minute low-frequency rTMS that was applied to the non-lesional hemisphere and 120 minutes of intensive OT (one-on-one training and self-training). MAIN OUTCOME MEASURES: Motor function of the affected upper limb was evaluated with the Fugl-Meyer Assessment and the Wolf Motor Function Test (WMFT) on the days of admission and discharge. WMFT performance time data were log-transformed. RESULTS: The Fugl-Meyer Assessment score increased significantly in all patients (from 40.2 ± 12.2 to 43.4 ± 11.8 points, P < .001), but the score increase was significantly larger in the Stage 4 group than in the other two groups (2.1 ± 2.3 points in the Stage 3 group, 5.1 ± 2.9 points in the Stage 4 group, and 2.3 ± 1.8 points in the Stage 5 group, all P < .05). Similarly, the WMFT performance time decreased significantly in all patients (from 3.27 ± 0.90 to 2.96 ± 1.10, P < .001), but the difference in the extent of the decrease was significant between Stage 3 and Stage 4 groups and between Stage 3 and Stage 5 groups (0.04 ± 0.07 in the Stage 3 group, 0.41 ± 0.29 in the Stage 4 group, and 0.35 ± 0.31 in the Stage 5 group, all P < .01). CONCLUSIONS: Our 15-day protocol of low-frequency rTMS and intensive OT is potentially promising in improving motor function of the affected upper limb. The extent of motor improvement by the intervention seemed to be influenced by the severity of upper limb hemiparesis at study entry.

Anti-spastic effect of low-frequency rTMS applied with occupational therapy in post-stroke patients with upper limb hemiparesis.

OBJECTIVE: To determine the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with occupational therapy (OT) on the spasticity of the hemiparetic upper limb after stroke. SUBJECTS AND METHODS: The study subjects were 39 post-stroke patients with spastic upper limb hemiparesis (age: 56.5 ± 16.0 years, time after onset: 50.3 ± 37.8 months). At admission, the severity of hemiparesis was categorized as Brunnstrom stage 3-5 for hand-fingers. During 15-day hospitalization, each patient received 22 sessions of low-frequency rTMS applied to the non-lesional hemisphere and OT (one-to-one training and self-training). The spasticity of finger and wrist flexors of the affected upper limb was evaluated using the modified Ashworth scale (MAS) on the day of admission and discharge and 4 weeks after discharge. Each subject underwent Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT). RESULTS: The low-frequency rTMS/OT protocol significantly decreased the MAS scores for both finger and wrist flexors at discharge and at 4 weeks after discharge. In addition, the low-frequency rTMS/OT protocol significantly increased the FMA score and shortened the WMFT performance time. CONCLUSIONS: The 15-day in-patient protocol of low-frequency rTMS/OT is potentially suitable for reducing spasticity as well as improving motor function on the affected upper limb after stroke.

Combination treatment of low-frequency rTMS and occupational therapy with levodopa administration: an intensive neurorehabilitative approach for upper limb hemiparesis after stroke.

The combination treatment of low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy was applied with concomitant oral administration of levodopa in five post-stroke patients with upper limb hemiparesis (age at treatment: 56-66 years; interval between onset of stroke and treatment: 18-143 months) as a 15-day inpatient protocol. Daily levodopa administration of 100 mg was initiated 1 week before admission and continued until 4 weeks after discharge. Low-frequency rTMS of 1 Hz was applied to the contralesional hemisphere for 40 min daily (two 20-min sessions) combined with intensive occupational therapy consisting of 60-min one-on-one training and 60-min self-exercise. Motor function of the affected upper limb was serially evaluated with the Fugl-Meyer Assessment and the Wolf Motor Function Test. At the end of the treatment, all patients showed improved motor function in the affected upper limbs. In some patients, the improvement was maintained until 4 weeks after discharge. No patient showed any adverse effect from the intervention. Our proposed protocol featuring levodopa administration, low-frequency rTMS, and intensive occupational therapy could provide a safe and feasible intervention for upper limb hemiparesis after stroke.

Low-frequency rTMS combined with intensive occupational therapy for upper limb hemiparesis after brain tumour resection.

OBJECTIVE: To assess the safety, feasibility and efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with occupational therapy (OT) in a hemiparetic patient who had undergone brain tumour resection. PARTICIPANT: A 39-year-old right-handed woman underwent brain tumour resection and presented 5 years later with right upper limb hemiparesis. At admission, she was considered to have reached a probable plateau state of motor functional recovery of the affected upper limb in spite of conventional occupational therapy. INTERVENTION: Low-frequency rTMS with 1 Hz applied to the right primary motor cortex followed by intensive occupational therapy (one-on-one training and self-training) was provided daily during the 15-day hospitalization. MAIN OUTCOME MEASURES: Fugl-Meyer Assessment and Wolf Motor Function Test were conducted serially to evaluate motor function on the affected upper limb. RESULTS: Neither adverse effect nor deterioration of neurological symptoms was recognized during the treatment period. The 15-day combination protocol improved motor function of the right upper limb and further improvement was noted 4 weeks after discharge. CONCLUSION: The proposed protocol of low-frequency rTMS with intensive occupational therapy is a potentially useful rehabilitative programme for upper limb hemiparesis after brain tumour resection.

Low-frequency repetitive transcranial magnetic stimulation and intensive occupational therapy for poststroke patients with upper limb hemiparesis: preliminary study of a 15-day protocol.

The purpose of the study was to determine the safety and feasibility of a 15-day protocol of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with intensive occupational therapy (OT) on motor function and spasticity in hemiparetic upper limbs in poststroke patients.Fifteen poststroke patients (age at study entry 55 ± 17years, time after stroke 57± 55 months) with upper limb hemiparesis categorized as Brunnstrom stages 3­5 forhand­fingers were recruited. They were considered to have reached a plateau state at study entry, based on the lack of any increase in Fugl­Meyer Assessment (FMA) Score inthe last 3 months. During the 15-day hospitalization, each patient received 22 sessions of rTMS with 1 Hz applied to the contralesional cerebral hemisphere, followed by intensive OT (one-to-one training including shaping techniques and self training). Upper limb motor function was evaluated by FMA and Wolf Motor Function Test at admission and discharge. The spasticity of finger flexors,wrist flexors and elbow flexors in the affected upper limb was also evaluated with Modified Ashworth Scale. The15-day protocol was well tolerated by all patients. Atdischarge, the FMA Score was increased in all 15 patients(17­57 to 18­61 points). Shortening of performance time on Wolf Motor Function Test was noted in 12 patients(44­1584 to 39­1485 s). The Modified Ashworth ScaleScore for some flexor muscles decreased in 12 patients.In conclusion, our 15-day protocol of low-frequency rTMS combined with intensive OT seems feasible not only for improving motor function, but also for reducing spasticity in the affected upper limb in post stroke hemiparetic patients.

Six-day course of repetitive transcranial magnetic stimulation plus occupational therapy for post-stroke patients with upper limb hemiparesis: a case series study.

PURPOSE: To clarify the safety and feasibility of a 6-day protocol of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with intensive occupational therapy (OT) for upper limb hemiparesis. METHODS: In-hospital combination treatment was provided for 5 post-stroke patients with upper limb hemiparesis after more than 12 months of the onset of stroke. Over 6 consecutive days, each patient received 10 sessions of combination treatment with 1 Hz rTMS and intensive OT (one-on-one training and self-training). Motor function in the affected upper limb was evaluated by Fugl-Meyer Assessment (FMA), Wolf Motor Function Test (WMFT), Ten-Second Test at admission, discharge, and 4 weeks after treatment. RESULTS: All patients completed the 6-day treatment protocol and none showed any adverse effects throughout the treatment. At the end of treatment, improvements in the scores of FMA, WMFT, and Ten-Second Test were found in all patients. No deterioration of improved upper limb function was observed at 4 weeks after the treatment. CONCLUSIONS: Our proposed protocol of combination treatment seems to be safe and feasible for post-stroke patients with upper limb hemiparesis, although the efficacy of the protocol needs to be confirmed in a large number of patients.