Predicting shoulder function after constraint-induced movement therapy: a retrospective cohort study

Background Several predictors have been associated with upper extremity (UE) recovery after stroke, but characteristics that predict shoulder function after constraint-induced movement therapy (CIMT) have not yet been identified.

Objectives To identify predictors associated with satisfactory shoulder function in patients with reduced shoulder function at admission to CIMT.

Methods One hundred and seventy five patients were treated using CIMT while in a specialized inpatient hospital. Satisfactory shoulder function was defined according to the functional ability scale of the Wolf Motor Function test. Predictors of satisfactory shoulder function after CIMT were identified using multivariable logistic regression.

Results Better distal arm function and good proximal shoulder function on admission to CIMT were strong predictors of satisfactory shoulder function, while age and time of admission to CIMT since stroke were not. Seventeen percent of all CIMT-participants with reduced shoulder function pre-CIMT reached a level of satisfactory shoulder function after CIMT.

Discussion A substantial part of patients with reduced shoulder function reached a level of satisfactory shoulder function after CIMT. Intensive CIMT training, comprising tasks that require both distal and proximal UE function, may increase shoulder function in patients with a potential functional reserve.     

A one-year follow-up after modified constraint-induced movement therapy for chronic stroke patients with paretic arm: a prospective case series study

Abstract

Background:

Despite the confirmed short-term effects of constraint-induced movement therapy, the long-term effects have not been sufficiently verified in terms of functional improvement of the affected arm.

Objective:

To evaluate the long-term effects and relationship between arm use in activities of daily living and arm improvement with modified constraint-induced movement therapy in chronic stroke patients.

Methods:

At 1 year after completing modified constraint-induced movement therapy, arm function (Fugl-Meyer Assessment) and amount of daily arm use (motor activity log) were assessed.

Results:

Fourteen post-stroke patients with mild to moderate impairment of arm function were analyzed. One year after completing modified constraint-induced movement therapy, participants consistently showed improvements in arm function and amount of daily arm use (analysis of variance: Fugl-Meyer Assessment, P?<?0.001; Motor Activity Log, P?<?0.001). For the Fugl-Meyer Assessment, post-hoc tests detected significant improvements (pre versus post, P?=?0.009; pre versus 1 year, P?<?0.0001; post versus 1 year, P?<?0.036). For the Motor Activity Log, post-hoc tests also detected significant improvements (pre versus post, P?=?0.0001; pre versus 1 year, P?<?0.0001; post versus 1 year, P?=?0.0014). The magnitude of the change in Fugl-Meyer Assessment score correlated significantly with the change in Motor Activity Log score (R?=?0.778, P?=?0.001).

Conclusions:

Among post-stroke patients with mild to moderate impairments of arm function, modified constraint-induced movement therapy without any other rehabilitation after intervention may improve arm function and increase arm use for 1 year. In addition, increasing arm use may represent an important factor in improving arm function, and vice versa.     

Stability of stereognosis after pediatric repetitive transcranial magnetic stimulation and constraint-induced movement therapy clinical trial

Objective: Poor sensibility affecting stereognosis, the ability to discriminate objects without visual input, can potentiate disuse of the paretic limb following stroke. The purpose of this study was to examine potential change in stereognosis after intervention. Methods: Stereognosis testing in a secondary subgroup of 10 children with hemiparesis and baseline stereognosis deficits (ages 11–16) after a 13-day clinical trial of real or sham repetitive transcranial magnetic stimulation (rTMS) and constraint-induced movement therapy (CIMT) is reported. All children received 10 h of CIMT while wearing a cast full-time. Results: Post-trial, 80% of participants from both intervention groups demonstrated improvement in stereognosis (95% CI: 44.4%–97.5%). Pre-trial to long-term follow-up (range: 21–57 months), 60% retained gains or improved (95% CI: 26.2%–87.8%). Between-group differences were not detected. Discussion: Children demonstrated stereognosis change following intervention. Research on this change and potential minimal clinically important differences are indicated.     

Improved quality of life following constraint-induced movement therapy is associated with gains in arm use,but not motor improvement

Background. Constraint-induced movement therapy (CI therapy) is one of few treatments for upper extremity (UE) hemiparesis that has been shown to result in motor recovery and improved quality of life in chronic stroke. However, the extent to which treatment-induced improvements in motor function versus daily use of the more affected arm independently contribute to improved quality of life remains largely unexplored.

Objective. The objective of this study is to identify whether motor function or daily use of a hemiparetic arm has a greater influence on quality of life after CI therapy.

Methods. Two cohorts of participants with chronic stroke received either in-person CI therapy (n = 29) or video-game home-based CI therapy (n = 16). The two cohorts were combined and the motor-related outcomes (Wolf Motor Function Test, Action Research Arm Test, Motor Activity Log [MAL]) and quality of life (Stroke-Specific Quality of Life) were jointly modeled to assess the associations between outcomes.

Results. The only outcome associated with improved quality of life was the MAL. Improvements in quality of life were not restricted to motor domains, but generalized to psychosocial domains as well.

Conclusions. Results suggest that improved arm use during everyday activities is integral to maximizing quality of life gains during motor rehabilitation for chronic post-stroke UE hemiparesis. In contrast, gains in motor function were not associated with increases in quality of life. These findings further support the need to implement techniques into clinical practice that promote arm use during daily life if improving quality of life is a main goal of treatment.

ClinicalTrials.gov Registration Numbers: NCT01725919 and NCT03005457     

Study to assess the effectiveness of modified constraint-induced movement therapy in stroke subjects: A randomized controlled trial

Background and Purpose:

The purpose of this study was to assess the effectiveness of modified constraint induced movement therapy (m-CIMT) in stroke subjects.

Materials and Methods:

A total of forty sub-acute stroke subjects were randomly assigned to either a m-CIMT (n = 20) or in a control group (n = 20). The m-CIMT group (14 men, 6 women; mean age = 55.2 years) consisted of structured 2 h therapy sessions emphasizing affected arm use, occurring 5 times/week for 2 weeks. A mitt was used to restrain the unaffected arm for 10 h/day for 2 week. The control group (11 men, 9 women; mean age = 56.4 years) consisted of conventional rehabilitation for time-matched exercise program. The outcome measures were evaluated at pre- and post-intervention by using the Wolf Motor Function Test (WMFT) and Fugl-Meyer assessment (FMA) of motor recovery after stroke.

Results:

After intervention significant effects were observed in m-CIMT group on WMFT (pre-test and post-test score was 28.04 ± 6.58, 13.59 ± 2.86; P =0.003). Similarly on FMA (pre- and post-test score was 31.15 ± 6.37, 55.7 ± 6.4; P = 0.00).

Conclusion:

There is a significant improvem ent in upper extremity function so it indicates that m-CIMT is effective in improving the motor function of the affected arm in stroke subjects. However, its long-term effect has not proved since there was no follow-up after intervention.     

Changes in diffusion tensor tractographic findings associated with constraint-induced movement therapy in young children with cerebral palsy

ObjectiveThe objective of the study was to determine whether constraint-induced movement therapy (CIMT) could lead to changes in diffusion tensor tractography (DTT) associated with clinical improvement in young children with unilateral cerebral palsy (CP).MethodsA standardized pediatric CIMT protocol (4 weeks, 120 h of constraint) was used on 10 children with unilateral CP who were younger than 5 years. DTT was performed in five participants before and after the intervention. Clinical outcome was measured by using the Pediatric Motor Activity Log (PMAL), Quality of Upper Extremity Skills Test (QUEST), and self-care domain of the Pediatric Evaluation of Disability Inventory.ResultsIn two patients, the affected corticospinal tract (CST) visible on pretreatment DTT became more prominent on posttreatment DTT. In one patient, the affected CST was not visible on pretreatment DTT, but was visible on posttreatment DTT. All the clinical outcomes significantly improved in the CIMT group compared with the control group. Changes in the PMAL how often scale (PMAL-HO) score significantly differed between the CIMT and control groups.ConclusionsChanges in the properties of the affected CST on DTT were accompanied with improved arm function after CIMT in the children with CP.SignificanceCIMT might lead to CST reorganization in young children with CP.     

Intracranial transplantation of monocyte-derived multipotential cells enhances recovery after ischemic stroke in rats

Cell transplantation has emerged as a potential therapy to reduce the neurological deficits caused by ischemic stroke. We previously reported a primitive cell population, monocyte-derived multipotential cells (MOMCs), which can differentiate into mesenchymal, neuronal, and endothelial lineages. In this study, MOMCs and macrophages were prepared from rat peripheral blood and transplanted intracranially into the ischemic core of syngeneic rats that had undergone a left middle cerebral artery occlusion procedure. Neurological deficits, as evaluated by the corner test, were less severe in the MOMC-transplanted rats than in macrophage-transplanted or mock-treated rats. Histological evaluations revealed that the number of microvessels that had formed in the ischemic boundary area by 4 weeks after transplantation was significantly greater in the MOMC-transplanted rats than in the control groups. The blood vessel formation was preceded by the appearance of round CD31(+) cells, which we confirmed were derived from the transplanted MOMCs. Small numbers of bloodvessels incorporating MOMC-derived endothelial cells expressing a mature endothelial marker RECA-1 were detected at 4 weeks after transplantation. In addition, MOMCs expressed a series of angiogenic factors, including vascular endothelial growth factor, angiopoetin-1, and placenta growth factor (PlGF). These findings provide evidence that the intracranial delivery of MOMCs enhances functional recovery by promoting neovascularization in a rat model for ischemic stroke.     

Effects of constraint-induced movement therapy on brain glucose metabolism in a rat model of cerebral ischemia: a micro PET/CT study

Purpose: Constraint-induced movement therapy (CIMT) can improve motor functions in stroke patients and ischemic rats. This study examined the effect of CIMT in ischemic rats using positron emission tomography (PET).

Methods: We used middle cerebral artery occlusion (MCAO) procedure to induce cerebral ischemia in rats. Male rats were divided into a negative control group (Normal, n = 4), a sham-operated group (Sham, n = 6), an ischemic group (Control, n = 6) and an ischemic CIMT-treated group (CIMT, n = 6). CIMT started at postoperative day 8 (d8) and lasted for 2 weeks. We utilized 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) micro PET/CT imaging to evaluate glucose metabolism in different brain regions at baseline, before, and after treatment, respectively.

Results: CIMT improved behavioral performance in the ischemic CIMT group. At the end of treatment, the CIMT group showed lower standardized uptake values (SUVs) in the ipsilateral cingulate, motor and somatosensory cortex, respectively; as well as the anterodorsal hippocampus compared to the Control group (1.80% ± 0.10% vs. 1.92% ± 0.08%, 1.32% ± 0.14% vs. 1.48% ± 0.09%, 1.18% ± 0.14% vs. 1.42% ± 0.15%, 1.68% ± 0.09% vs. 1.79% ± 0.06%, P < 0.05). We also observed higher SUVs in the acbcore shell and cortex insular of the contralateral hemisphere compared to the Control group (2.07% group in the acbcore shell and cortex insular of contralateral P < 0.05).

Conclusion: CIMT improved behavioral outcomes in cerebral ischemic rats and this effect can be attributed to increased glucose utilization in the contralateral hemisphere.     

Neurological recovery after decompressive craniectomy for massive ischemic stroke

Introduction: Decompressive craniectomy has demonstrated efficacy in reducing morbidity and mortality in critically ill patients with massive hemispheric cerebral infarction. However, little is known about the patterns of functional recovery that exist in patients after decompressive craniectomy, and controversy still exists as to whether craniotomy and infarct resection (“strokectomy”) are appropriate alternatives to decompression alone. We therefore used functional magnetic resonance imaging (f-MRI) to assess the extent and location of functional recovery in patients after decompressive craniectomy for massive ischemic stroke. Methods: f-MRI was obtained in three patients with massive nondominant cerebral infarction who had undergone decompressive craniectomy for severe cerebral edema 13 to 26 months previously. Brain activation was triggered by hand-gripping or foot-movement tasks. Imaging results were combined with periodic clinical follow-up to determine the extent of neurological recovery. Results: Activation of the contralateral hemisphere was seen in the sensorimotor cortex, premotor, and supplementary motor areas. Lesser activation patterns were seen in equivalent regions of the infarcted hemisphere. Peri-infarct activation foci were seen in two of the three patients, but no activation occurred within the area of infarction as defined by the initial stroke seen on diffusion-weighted MRI. All three patients demonstrated some corresponding neurological improvement. Conclusion: After massive hemispheric cerebral infarction requiring decompressive craniectomy, patients may experience functional recovery as a result of activation in both the infarcted and contralateral hemispheres. The evidence of functional recovery in peri-infarct regions suggests that decompression alone may be preferable to strokectomy where the risk of damage to adjacent nonischemic brain may be greater.     

Neurofunctional changes after a single mirror therapy intervention in chronic ischemic stroke

Background: Mirror therapy (MT) is becoming an alternative rehabilitation strategy for various conditions, including stroke. Although recent studies suggest the positive benefit of MT in chronic stroke motor recovery, little is known about its neural mechanisms.

Purpose: To identify functional brain changes induced by a single MT intervention in ischemic stroke survivors, assessed by both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI).

Materials and methods: TMS and fMRI were used to investigate 15 stroke survivors immediately before and after a single 30-min MT session.

Results: We found statistically significant increase in post-MT motor evoked potential (MEP) amplitude (increased excitability) from the affected primary motor cortex (M1), when compared to pre-MT MEP. Post-MT fMRI maps were associated with a more organized and constrained pattern, with a more focal M1 activity within the affected hemisphere after MT, limited to the cortical area of hand representation. Furthermore, we find a change in the balance of M1 activity toward the affected hemisphere. In addition, significant correlation was found between decreased fMRI β-values and increased MEP amplitude post-MT, in the affected hemisphere.

Conclusion: Our study suggests that a single MT intervention in stroke survivors is related to increased MEP of the affected limb, and a more constrained activity of the affected M1, as if activity had become more constrained and limited to the affected hemisphere.     

基线血压水平与急性缺血性脑卒中早期降压治疗3个月结局的关系

目的 探讨基线血压水平与急性缺血性脑卒中早期降压治疗3 m结局关系.方法 收集2009年8月-2013年5月发病48 h内住院且经影像学确诊合并高血压的急性期缺血性脑卒中患者828例,根据入组时收缩压(Systolic Blood Pressure,SBP)水平分为140 ～ 160 mmHg组(n=276)、160～...     

Changes in effective connectivity of the primary motor cortex in stroke patients after rehabilitative therapy

We used a perturb-and-measure approach, by combining transcranial magnetic stimulation (TMS) and positron emission tomography (PET), to examine changes in the primary motor area (M1) and its effective connectivity in stroke patients with chronic motor deficits (>1-year post-stroke) who underwent 3 weeks of constraint-induced movement therapy. During the 3-week period, 7 patients spent 4 h per day performing shaping exercises with the affected arm under our supervision for 14 days and wore a mitt on the unaffected arm at home in situations where safety was not compromised. Anatomical magnetic resonance imaging confirmed that all patients had lesions that encompassed the white matter; no patient had damage in the hand representation of M1. Improvements on various motor tests were observed immediately after therapy and 1 month afterwards. During the TMS/PET sessions, we applied trains of subthreshold 10-Hz repetitive TMS over the hand representation of the ipsilesional and contralesional M1s and varied the number of TMS trains delivered during each scan. The results demonstrate changes in the local response of TMS in the ipsilesional and contralesional M1, changes in the strength of interhemispheric connectivity between M1s, and changes in the effective connectivity of the ipsilesional and contralesional M1s with the non-primary motor areas, the basal ganglia, and the motor nuclei of the thalamus.     

Thrombolysis and reperfusion: advanced understanding of early management strategies in acute ischemic stroke

Abstract

Currently, intravenous (IV) thrombolysis within 3 hours from stroke onset is the only approved treatment in acute ischemic stroke (AIS). Although effective, the definition of therapeutic time window and appropriate patient selection still remains controversial. Notably, early endovascular treatment strategies may serve as an adjunct therapy for time window extension in AIS.

In this article, we review the safety and efficacy of IV thrombolysis in AIS as it pertains to the optimal time window, the selection of eligible patients, and in combination with endovascular treatment. Combined clinical application of IV thrombolysis and endovascular therapy may improve the therapeutic outcomes for AIS patients.     

Autologous bone marrow mononuclear cells enhance recovery after acute ischemic stroke in young and middle-aged rats

We investigated intra-arterially administered autologous bone marrow mononuclear cells (MNCs) in rats with acute ischemic stroke. Long Evans rats (2 to 3 months or 12 months old) underwent tandem reversible common carotid artery (CCA)/middle cerebral artery (MCA) occlusion (CCAo/MCAo) for 3 h and then 24 h later underwent tibial bone marrow harvest. Ten million or 4 million cells were re-injected by an intra-carotid infusion. Control animals underwent marrow needle insertion and then saline injection into the carotid artery. Animals were assessed on a battery of neurological tests. MNCs in the ischemic brain were tracked using Q-dot nanocrystal labeling. Infarct volume and cytokines in the ischemia-affected brain were analyzed. Cell-treated animals in the younger and older groups showed improvement from 7 to 30 days after stroke compared with vehicle-treated animals. MNCs significantly reduced infarct volume compared with saline. There was a significant reduction in tumor necrosis factor-α, interleukin-1α (IL-1α), IL-β, IL-6, and a significant increase in IL-10 in injured brains harvested from the cell-treated groups compared with saline controls. Labeled MNCs were found in the peri-infarcted area at 1 h and exponentially decreased over the ensuing week after injection. Autologous bone marrow MNCs can be safely harvested from rodents after stroke, migrate to the peri-infarct area, enhance recovery, and modulate the post-ischemic inflammatory response.     

中西医结合疗法对缺血性卒中恢复期患者运动功能的影响

目的观察中西医结合疗法及康复疗法对缺血性卒中恢复期患者运动功能的影响。方法入选64例患者,分别予以中西医结合治疗(n=32例)和康复治疗(n=32例),分别于治疗期(入组当天、2周和4周)及随访期(3月末和6月末),用FuglMeyer简式运动功能评分(FMA)评价患者的运动功能。对不同时点的不同治疗疗效进行分析和比较。结果重复测量方差分析显示时间因素有显著统计学差异(P=0.000),分组因素无显著统计学差异(P=0.562)。结论中西医结合疗法和现代康复疗法均能提高缺血性卒中恢复期患者的运动功能,疗效相当。     

Functional magnetic resonance imaging evaluation of brain function reorganization in cerebral stroke patients after constraint-induced movement therapy

In this study, stroke patients received constraint-induced movement therapy for 3 weeks. Before and after constraint-induced movement therapy, the flexibility of their upper limbs on the affected side was assessed using the Wolf motor function test, and daily use of their affected limbs was assessed using the movement activities log, and cerebral functional reorganization was assessed by functional magnetic resonance imaging. The Wolf motor function test score and the movement activities log quantity and quality scores were significantly increased, while action performance time in the Wolf motor function test was significantly decreased after constraint-induced movement therapy. By functional magnetic resonance imaging examination, only scattered activation points were visible on the affected side before therapy. In contrast, the volume of the activated area was increased after therapy. The activation volume in the sensorimotor area was significantly different before and after therapy, and the activation area increased and appeared adjusted. In addition to the activated area around the lesions being decreased, there were also some new activated areas, including the supplementary movement area, premotor area and the ipsilateral sensorimotor area. Our findings indicate that constraint-induced movement therapy significantly improves the movement ability and daily use of the affected upper limbs in stroke patients and promotes cerebral functional reorganization.     

Functional reorganization and recovery after constraint-induced movement therapy in subacute stroke: case reports

Preliminary assessments of the feasibility, safety, and effects on neuronal reorganization measured with transcranial magnetic stimulation (TMS) from Constraint-Induced Movement Therapy (CIMT) of the upper extremity were made in eight cases of subacute stroke. Within fourteen days of their stroke, patients were randomly assigned to two weeks of CIMT or traditional therapy. Baseline motor performance and cortical/subcortical representation for movement with TMS were assessed before treatment. Post-treatment assessments were made at the end of treatment and at three months after the stroke. The TMS mapping showed a larger motor representation in the lesioned hemisphere of the CIMT patients as compared to the controls at the three-month follow-up assessment. The enlarged motor representation in the lesioned hemisphere for hand movement correlated with improved motor function of the affected hand, suggesting a link between movement representation size as measured with TMS and functionality. These results suggest that TMS can be safely and effectively used to assess brain function in subacute stroke and further suggest that CIMT may enhance cortical/subcortical motor reorganization and accelerate motor recovery when started within the first two weeks after stroke.     

Therapeutic effects of lipo-prostaglandin E1 on angiogenesis and neurogenesis after ischemic stroke in rats

Previous studies have demonstrated that prostaglandin E1 (PGE1) has a neuroprotective effect on cerebral ischemia. However, it remains unknown whether PGE1 promotes angiogenesis and neurogenesis after ischemic stroke. In this study, adult male Sprague-Dawley rats were subjected to permanently distal middle cerebral artery occlusion (MCAO). Rats were treated with lipo-prostaglandin E1(lipo-PGE1, 10 μg/kg/d) or the same volume of 0.9% saline starting 24 hours after MCAO daily for 6 consecutive days. All rats were injected 5'-bromo-2'-deoxyuridine (BrdU, 50 mg/kg) intraperitoneally every 12 hours for 3 consecutive days before being sacrificed. At 7 and 14 days after MCAO or sham-operation, rats were sacrificed. Post-stroke neurological outcome, infarction volume, angiogenesis and neurogenesis were evaluated. Treatment with lipo-PGE1 significantly increased the vascular density in the peri-infarct areas at 7 and 14 days after MCAO. The lipo-PGE1 treatment significantly enhanced the proliferation and migration of endogenous neural stem cells in the ipsilateral subventricular zone. The neural stem cells associated with blood vessels closely within a neurovascular niche in lipo-PGE1-treated rats after stroke. The lipo-PGE1 treatment also significantly improved the neurological recovery after MCAO. These results indicate that treatment with lipo-PGE1 promotes post-stroke angiogenesis, neurogenesis and their interaction, which would contribute to neurological recovery after cerebral infarction. Our study provides novel experimental evidences for the neuroprotective roles of PGE1 in ischemic stroke.