Human Spinal Circuit Plasticity with Locomotor Training in SCI

描述(由申请人提供)： 目的：本研究旨在探讨运动不完全性脊髓损伤(SCI)后与运动训练相关的人类脊髓神经回路可塑性，并确定这种可塑性与步态功能恢复程度之间的关系。研究计划-在拟议的研究中，我们将研究亚急性运动不完全脊髓损伤的受试者，在一个机器人运动训练课程之前、期间和之后的3个月。我们将通过H反射测试来评估脊髓反射回路的功能，并将其与地面步态的功能恢复进行比较。我们研究了在3个月的运动训练前后比目鱼肌中的H反射，发现在地面步速恢复相对较快的患者中，这些反射减少或“正常化”，但在仅比地面步速恢复较慢的患者中，这些反射实际上增加了。我们感兴趣的是确定这些患者的反射变化的时间进程，并找出如果患者恢复了较快的步速和更正常的反射，当他们只实现较慢的步速时，他们是否首先经历了相对增加的多柔韧性。这将表明我们应该对那些恢复步速较慢的人进行更长时间的训练。我们还建议同时研究其他腿部肌肉的H反射，以确定比目鱼肌H反射恢复模式是否适用于所有的下肢肌肉。方法-一旦患者符合纳入/排除标准并提供知情同意，他们将被安装并定向到机器人步态矫形器、Lokomat和该设备中的运动训练。在4个月的运动训练前、月中和3个月后，对患者进行电生理和临床步态恢复评估。功能步态测量将包括在10米步行过程中测量的速度，以及使用GAITRite系统记录步幅长度和站立宽度等参数的步态测量。将使用一种新技术进行电生理测试，以在多个下肢肌肉中同时产生H反射。刺激腰背根在所有腿部肌肉中产生这些“背根运动电位”，并可在运动训练的不同条件下在同一时间点进行研究，同时采取步态措施。具体地说，我们将在Lokomat中研究两种不同跑步机速度和两种不同体重支撑下的背根运动电位。一旦采取了基线的电生理和功能步态措施，患者将开始在Lokomat进行为期16周的运动训练。随着时间的推移，随着时间的推移，运动训练速度会提高，而BWS会在患者能够承受的范围内降低。一旦训练开始，功能性步态测量和电生理测试将每4周进行一次，每两周错开进行一次。也就是说，在训练开始后2、6、10和14周重复功能步态测量，在4、8、12和16周进行电生理测量。一旦患者完成了他们的运动训练，他们将被要求在3个月后返回进行后续的功能步态测量和电生理测试，以确定这些指标自训练以来是否随着时间的推移而发生变化。 公共卫生相关性： 脊髓损伤(SCI)发生在退伍军人身上，要求退伍军人医疗系统为这些退伍军人提供尽可能好的护理。运动疗法可以改善患有运动不完全性脊髓损伤的退伍军人的运动功能障碍，但我们不知道神经系统随着训练的变化，也不知道如果我们更好地了解导致康复的潜在神经可塑性，是否可以获得更好的训练效果和更好的恢复。希望更多关于运动训练改善运动不完全性脊髓损伤患者步态恢复的神经生理学机制的了解，将为如何改进治疗或为目前无法从运动训练中受益的脊髓损伤后患者提供新的治疗思路。

DESCRIPTION (provided by applicant): Objective - The proposed study is designed to investigate human spinal neural circuit plasticity associated with locomotor training following motor incomplete spinal cord injury (SCI) and determine the relationship between that plasticity and the extent of functional recovery of gait. Research Plan - In the proposed study we will study subjects with sub-acute motor incomplete SCI before, multiple times during, and 3 months following a course of robotic locomotor training. We will assess spinal reflex circuit functioning as measured by H reflex testing and compare that with functional recovery of over ground gait. We have studied H-reflexes in the soleus muscle during stepping before and after 3 months of locomotor training and found that those reflexes decrease or "normalize" in patients who recover relatively greater over ground gait speeds but that those reflexes actually increase in patients who only recover slower over ground gait speeds. We are interested in determining the time course of reflex changes in these patients and in finding out if patients who recover faster gait speeds and more normal reflexes first experience a relative increase in hypereflexia when they have only achieved slower gait speeds. This would indicate we should train those with slower recovered gait speeds for longer periods of time. We also propose to study H-reflexes simultaneously in other leg muscles to determine if the soleus H-reflex recovery pattern is common to all lower limb muscles or not. Methods - Once patients meet inclusion/exclusion criteria and provide informed consent, they will be fitted for and oriented to the robotic gait orthosis, the Lokomat, and locomotor training in that device. Before, monthly during and 3 months after 4 months of locomotor training, patients will be assessed electrophysiologically and by clinical measures of gait recovery. Functional gait measures will be speed, measured during a 10 meter walk, and stepping measurements using the GAITRite system to document parameters like stride length and stance width. Electrophysiological testing will be carried out with a new technique to generate simultaneous H reflexes in multiple lower limb muscles. Stimulation of the lumbar dorsal roots generates these "dorsal root motor potentials" in all leg muscles and can be studied under various conditions at the same time points during locomotor training as gait measures are taken. Specifically, we will study dorsal root motor potentials at two different treadmill speeds and at two different body weight supports in the Lokomat. Once baseline electrophysiological and functional gait measures have been taken, patients will begin 16 weeks of locomotor training in the Lokomat. Over time, the locomotor training speed will be increased and the BWS decreased as can be tolerated by the patient. Once training has begun, functional gait measurement and electrophysiological testing will occur every 4 weeks, staggered by two weeks. That is to say that at 2, 6, 10 and 14 weeks after training begins functional gait measures will be repeated and at 4, 8, 12 and 16 weeks, electrophysiological measures will be taken. Once patients have completed their locomotor training, they will be asked to return 3 months later for follow up functional gait measures and electrophysiological testing to determine whether those have changed over time since training. PUBLIC HEALTH RELEVANCE: Spinal cord injury (SCI) occurs in veterans and requires that the VA medical system delivers the best possible care for these veterans. Locomotor dysfunction can be improved with locomotor therapy in veterans with motor incomplete SCI but we do not know how the nervous system is changing with this training or whether we could get better training effects and better recovery if we better understood the underlying neural plasticity that gives rise to that recovery. Hopefully, learning more about the neurophysiological mechanisms by which locomotor training improves gait recovery in motor incomplete SCI will present new ideas about how to improve upon that treatment or offer treatment to patients that currently do not benefit from locomotor training after SCI.