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

项目摘要 在超过720万美国中风幸存者中，约有70%的人持续存在步态缺陷，包括 行走速度减慢，行走模式不对称，以及腿部协调性降低，这些都限制了他们的 社区活动的能力。目前的康复方法是基于这样的假设：中风 在保留脊髓的同时损害运动皮质功能，从而集中刺激同侧或 在步态训练中激活休眠或新通路的对侧运动皮质。尽管动物模型 中风显示颈椎和腰椎脊髓继发性变性，表明 脊髓可能影响功能恢复，很少或根本没有研究来阐明脊髓的变化 在中风后的人类身上。我们的目的是评估脊柱刺激结合步态训练的效果。 中风后，并研究这些影响的潜在机制。在前期工作中，我们测量了脊椎 无创经皮脊髓电刺激诱发运动电位10例 卒中幸存者、10名年龄匹配的健康对照组和10名年轻的健康受试者。刺激阈值为 卒中幸存者显著高于对照组，偏瘫侧潜伏期显著延长 与非瘫痪侧相比，表明中风对下游脊髓回路和 下行通道。我们还比较了脊髓刺激+对称步态训练(n=4) 单独进行步态训练(n=4)，显著改善步长对称性、步行速度(10米步行测试， 10MWT)和步行耐力(6分钟步行测试，6MWT)；这些改善超过了最低限度 对慢性卒中有重要的临床意义。这些结果支持了我们的假设，即脊髓刺激可能 提高步态训练效能。在目标1中，我们将评估脊柱刺激和假手术的短期效果。 无论是否进行对称步态训练，对步态功能的刺激(主要结果：步长 对称性)和皮质脊髓环路对25名中风幸存者的影响。在目标2中，我们将进行随机临床试验 对称性步态训练加刺激法和假刺激法治疗中风的远期疗效 幸存者(n=25)。主要结果将是步长对称；次要结果包括 时间步态对称性、速度(10MWT)、肌肉激活(肌电图)、步行耐力(6MWT)、 能量消耗(COSMED K4B2)、上肢和下肢功能(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)。我们还将调查 脊髓刺激效应的机制研究--通过检测以下肢体肌肉中诱发的SIMPS 皮质/皮质下对皮质脊髓轴突的刺激和皮质内抑制。这项工作将(I)识别短小- 和脊柱刺激的长期效果，(Ii)证实脊柱刺激是一种非侵入性的恢复方法 慢性中风的步态，(Iii)确定可能决定对脊柱刺激的反应的临床措施，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。

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.