Locomotor function following transcutaneous electrical spinal cord stimulation in individuals with hemiplegic stroke

偏瘫中风患者经皮脊髓电刺激后的运动功能

基本信息

批准号：
10280231
负责人：
Arun Jayaraman
金额：
$ 73.69万
依托单位：
REHABILITATION INSTITUTE OF CHICAGO D/B/A SHIRLEY RYAN ABILITYLAB
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-12 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10280231
关键词：
Acute Address Affect Age Animal Model Area Axon Biomechanics Brain Cervical Chronic Clinical Clinical Trials Communities Contracture Contralateral Custom Data Dose Educational Intervention Effectiveness Electric Stimulation Electromyography Electrophysiology (science)Energy Metabolism Functional disorder Gait Gait abnormality Gait speed Goals H-Reflex Health Health Status Heart Rate Hemiplegia Human Impairment Individual Intervention Ipsilateral Length Long-Term Effects Lower Extremity Lumbar spinal cord structure Measures Mental Depression Methods Motor Motor Activity Motor Cortex Motor Evoked Potentials Motor Neurons Movement Muscle Muscle Weakness Neural Pathways Neurologic Neurostimulation procedures of spinal cord tissue Outcome Measure Paresis Participant Pathway interactions Pattern Performance Peripheral Persons Physiological Protocols documentation Publishing Quality of life Randomized Randomized Clinical Trials Recovery of Function Rehabilitation therapy Research Side Site Speed Spinal Spinal Cord Spinal cord injury Stroke System Techniques Testing Therapeutic Time Training Transcranial magnetic stimulation Transcutaneous Electric Nerve Stimulation Upper Extremity Vertebral column Volition Walking Wallerian Degeneration Work actigraphy base chronic stroke experience experimental study gait rehabilitation gait symmetry improved kinematics meter motor control motor impairment neuroregulation noninvasive brain stimulation physical therapist placebo group post stroke preservation primary outcome response restoration secondary outcome spasticity spatiotemporal spinal pathway spinal reflex stroke model stroke patient stroke survivor targeted treatment tool treadmill treatment site walking speed wearable sensor technology

项目摘要

Project Abstract Approximately 70% of the more than 7.2 million U.S. stroke survivors experience persistent gait deficits, including reduced walking speed, asymmetrical walking patterns, and reduced lower limb coordination, which limit their capacity for community ambulation. Current rehabilitation approaches are based on the assumption that stroke impairs motor cortex function while the spinal cord is preserved and thus focus on stimulating the ipsilateral or contralateral motor cortex during gait training to activate dormant or new pathways. Although animal models of stroke reveal secondary degeneration of the cervical and lumbar spinal cord, suggesting that damage to the spinal cord may effect functional recovery, little or no research has been done to elucidate spinal cord changes in humans after stroke. Our objective is to evaluate the effects of spinal stimulation combined with gait training after stroke and to investigate mechanisms underlying these effects. In preliminary work, we measured spinally evoked motor potentials (sEMPs) generated by non-invasive, transcutaneous electrical spinal stimulation in 10 stroke survivors, 10 age-matched healthy controls, and 10 young healthy subjects. Stimulation thresholds were significantly higher in stroke survivors than in controls and latency was significantly delayed in the paretic side compared to the non-paretic side, indicating secondary effects of stroke on downstream spinal circuitry and descending pathways. We also showed that spinal stimulation + symmetry-focused gait training (n=4) compared to gait training alone (n=4), significantly improved step-length symmetry, walking speed (10-meter walk test, 10MWT), and walking endurance (6-minute walk test, 6MWT); these improvements exceeded the minimal clinically important difference for chronic stroke. These results support our hypothesis that spinal stimulation may increase gait training efficacy. In Aim 1, we will evaluate the short-term effects of spinal stimulation and sham stimulation, with or without symmetry-focused gait training, on gait function (primary outcome: step-length symmetry) and corticospinal circuitry in 25 stroke survivors. In Aim 2, we will conduct a randomized clinical trial to evaluate the long-term effects of symmetry-focused gait training with stim or sham stimulation in stroke survivors (n=25 per group). The primary outcome will be step-length symmetry; secondary outcomes include temporal gait symmetry, speed (10MWT), muscle activation (electromyography), walking endurance (6MWT), energy expenditure (Cosmed K4B2), upper and lower limb function (Fugl-Meyer Assessment), health status (Stroke Impact Scale-16), and community activity (wearable sensors, Actigraph LLC). We will also investigate mechanisms underlying the effects of spinal stimulation by examining sEMPs elicited in lower limb muscles by cortical/subcortical stimulation of corticospinal axons and intracortical inhibition. This work will (i) identify short- and long-term effects of spinal stimulation, (ii) validate spinal stimulation as a non-invasive method to restore gait in chronic stroke, (iii) identify clinical measures that may determine response to spinal stimulation, and (iv) identify underlying neuromodulatory mechanisms, which may provide additional treatment options.

项目摘要美国超过 720 万中风幸存者中，约 70% 存在持续性步态缺陷，包括步行速度降低、步行模式不对称以及下肢协调能力下降，这些都限制了他们社区行走能力。目前的康复方法基于这样的假设：中风损害运动皮层功能，同时保留脊髓，因此专注于刺激同侧或步态训练期间对侧运动皮层激活休眠或新通路。虽然动物模型中风揭示了颈椎和腰椎脊髓的继发性变性，表明脊髓损伤脊髓可能会影响功能恢复，但很少或没有研究来阐明脊髓的变化人类中风后。我们的目标是评估脊柱刺激与步态训练相结合的效果中风后并研究这些影响的机制。在前期工作中，我们测量了脊柱通过非侵入性、经皮脊髓电刺激产生的诱发运动电位 (sEMP) 10 中风幸存者、10 名年龄匹配的健康对照者和 10 名年轻健康受试者。刺激阈值是中风幸存者中的潜伏期显着高于对照组，并且麻痹侧的潜伏期显着延迟与非麻痹一侧相比，表明中风对下游脊髓回路的继发影响下降的路径。我们还表明，脊柱刺激 + 对称性步态训练 (n=4) 与单独进行步态训练（n=4），显着改善步长对称性、步行速度（10米步行测试， 10MWT）和步行耐力（6分钟步行测试，6MWT）；这些改进超出了最低限度慢性中风的临床重要差异。这些结果支持我们的假设，即脊髓刺激可能提高步态训练效果。在目标 1 中，我们将评估脊髓刺激和假手术的短期效果刺激，有或没有以对称为中心的步态训练，对步态功能（主要结果：步长对称性）和 25 名中风幸存者的皮质脊髓回路。在目标2中，我们将进行一项随机临床试验评估刺激或假刺激的对称步态训练对中风的长期影响幸存者（每组 n=25）。主要结果是步长对称性；次要结果包括颞部步态对称性、速度 (10MWT)、肌肉激活（肌电图）、步行耐力 (6MWT)、能量消耗（Cosmed K4B2）、上下肢功能（Fugl-Meyer评估）、健康状况（中风影响量表-16）和社区活动（可穿戴传感器，Actigraph LLC）。我们也会调查通过检查在下肢肌肉中引起的表面电磁脉冲来研究脊髓刺激作用的潜在机制皮质脊髓轴突的皮质/皮质下刺激和皮质内抑制。这项工作将（i）识别短以及脊柱刺激的长期影响，(ii) 验证脊柱刺激作为一种非侵入性恢复方法慢性中风的步态，(iii) 确定可能确定对脊柱刺激反应的临床措施，以及 (iv) 确定潜在的神经调节机制，这可能提供额外的治疗选择。