中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (11): 2459-2464.doi: 10.4103/1673-5374.339012

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

神经根和皮质之间的配对相关磁刺激对脊髓损伤后的下肢运动功能的影响：一项随机对照试验方案

  

  • 出版日期:2022-11-15 发布日期:2022-04-22
  • 基金资助:
    国家重点研究发展计划(2020YFC2004202)、国家自然科学基金(81772453，81974358)、同济大学附属阳芝康复医院科研项目(KYPY202006)。

Effects of paired associative magnetic stimulation between nerve root and cortex on motor function of lower limbs after spinal cord injury: study protocol for a randomized controlled trial

Ting-Ting Sun1, #, Guang-Yue Zhu2, #, Ya Zheng2, Ye-Ran Mao3, Qi-Long Hu1, Gong-Ming Song1 , Rong Xu1, Qi Yang2, Dan Zhao2, Xu-Yun Hua4, 5, 6, *, Dong-Sheng Xu3, 4, 6, *   

  1. 1Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China; 2Rehabilitation Medical Center, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China; 3School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 4Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, China; 5Department of Traumatology and Orthopedics, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 6Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
  • Online:2022-11-15 Published:2022-04-22
  • Contact: Dong-Sheng Xu, MD, dxu0927@shutcm.edu.cn; Xu-Yun Hua, MD, swrhxy@126.com.
  • Supported by:
    This study was supported by the National Key Research and Development Program of China, No. 2020YFC2004202 (to DSX); the National Natural Science Foundation of China (General Program), Nos. 81772453, 81974358 (to DSX); Scientific Research Project of Yangzhi Rehabilitation Hospital Affiliated to Tongji University, No. KYPY202006 (to TTS).

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摘要：

经典的配对关联刺激提高目标突触的可塑性，其疗效已在动物试验和上肢脊髓损伤患者的临床试验中得到验证。相较于经典配对关联刺激，通过周围和中枢双靶点磁刺激形成关联配对刺激具有更好的可操作性，已有研究表明配对相关磁刺激(PAMS)可以促进脑卒中后的神经修复，但目前PAMS是否能促进脊髓损伤下肢运动功能障碍的恢复尚不明确。由于脊髓损伤后功能的恢复在很大程度上依赖于皮质脊髓束的神经传导，因此该试验的目的是通过运动诱发电位和体感诱发电位变化验证PAMS增强神经回路激活的效果，从而改善下肢运动功能和感觉功能和提高日常生活能力以及减少痉挛。验纳入中国康复医院脊髓损伤科胸椎创伤康复患者110例。受试者将以1:1的比例随机分配到2组，试验组55例采用PAMS与常规康复治疗结合治疗，而对照组55例采用常规康复治疗与假刺激配合治疗。试验的主要结局指标为基线至末次随访美国脊髓损伤协会脊髓神经功能评估表中的下肢运动功能评分的变化。次要结局指标包括基线至末次随访美国脊髓损伤协会脊髓神经功能评估表中的下肢感觉评分、运动诱发电位(MEP)、感觉诱发电位(SEP)、改良Ashworth量表(MAS)评分、Maslach倦怠量表(MBI)评分、汉密尔顿抑郁评定量表(HRSD)评分的变化。上述各指标主要观察时间点均包括基线、干预开始后 4 周，然后在第12和24 周进行随访，并在整个治疗及随访过程中记录不良事件。在结果指标中，MEP潜伏期反应了皮质脊髓束的传递时间，波幅反应了皮质脊髓束的募集能力，通过该结果指标可以体现在脊髓前角突触形成棘波时间依赖性可塑性(STDP)配对刺激提高突触效能的作用机制。作者希望试验结果证实，PAMS可促进脊髓损伤患者下肢感觉和运动功能的恢复，提高日常生活能力及减少痉挛；PAMS通过激活脊髓运动神经元的兴奋性和刺激突触可塑性来促进神经修复；PAMS可为改善脊髓损伤患者的运动康复提供一种新治疗方案。该试验的对象招募时间为2021-04，试验经中国同济大学附属养志康复医院伦理委员会批准，批准号：YZ2020-018，批准时间：2020-05-18。该方案已在中国临床试验注册中心注册，注册号：ChiCTR2100044794。方案版本号：1.0。试验将于2022年4月完成。

https://orcid.org/0000-0002-8477-5377 (Dong-Sheng Xu); https://orcid.org/0000-0002-2935-7551 (Xu-Yun Hua)

关键词: 刺激间期, 运动诱发电位, 改良Ashworth量表, Maslach倦怠量表, 可塑性, 重复经颅磁刺激, 配对相关磁刺激, 脊髓损伤, 感觉诱发电位, 棘波时间依赖性可塑性

Abstract: Classic paired associative stimulation can improve synaptic plasticity, as demonstrated by animal experiments and human clinical trials in spinal cord injury patients. Paired associative magnetic stimulation (dual-target peripheral and central magnetic stimulation) has been shown to promote neurologic recovery after stroke. However, it remains unclear whether paired associative magnetic stimulation can promote recovery of lower limb motor dysfunction after spinal cord injury. We hypothesize that the current caused by central and peripheral magnetic stimulation will converge at the synapse, which will promote synapse function and improve the motor function of the relevant muscles. Therefore, this study aimed to examine the effects of paired associative magnetic stimulation on neural circuit activation by measuring changes in motor evoked and somatosensory evoked potentials, motor and sensory function of the lower limbs, functional health and activities of daily living, and depression in patients with spinal cord injury. We will recruit 110 thoracic spinal trauma patients treated in the Department of Spinal Cord Injury, China Rehabilitation Hospital and randomly assign them to experimental and control groups in a 1:1 ratio. The trial group (n = 55) will be treated with paired associative magnetic stimulation and conventional rehabilitation treatment. The control group (n = 55) will be treated with sham stimulation and conventional rehabilitation treatment. Outcomes will be measured at four time points: baseline and 4, 12, and 24 weeks after the start of intervention (active or sham paired associative magnetic stimulation). The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last follow-up. Secondary outcome measures include changes in lower limb American Spinal Injury Association sensory function score, motor evoked potentials, sensory evoked potentials, modified Ashworth scale score, Maslach Burnout Inventory score, and Hamilton Depression Scale score over time. Motor evoked potential latency reflects corticospinal tract transmission time, while amplitude reflects recruitment ability; both measures can help elucidate the mechanism underlying the effect of paired associative magnetic stimulation on synaptic efficiency. Adverse events will be recorded. Findings from this trial will help to indicate whether paired associative magnetic stimulation (1) promotes recovery of lower limb sensory and motor function, reduces spasticity, and improves quality of life; (2) promotes neurologic recovery by increasing excitability of spinal cord motor neurons and stimulating synaptic plasticity; and (3) improves rehabilitation outcome in patients with spinal cord injury. Recruitment for this trial began in April 2021 and is currently ongoing. It was approved by the Ethics Committee of Yangzhi Affiliated Rehabilitation Hospital of Tongji University, China (approval No. YZ2020-018) on May 18, 2020. The study protocol was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2100044794) on March 27, 2021 (protocol version 1.0). This trial will be completed in April 2022.

Key words: interstimulus interval, motor-evoked potentials, Modified Ashworth Scale, Maslach Burnout Inventory, paired-associative magnetic stimulation, plasticity, repetitive transcranial magnetic stimulation, sensory-evoked potential, spinal cord injury, spike timing-dependent plasticity