A Double-Blind, Randomized, Controlled Trial of Epidural Conus Medullaris Stimulation to Alleviate Pain and Augment Rehabilitation in Patients with Subacute Thoracic Spinal Cord Injury (SCI)

摘要 脊髓损伤(SCI)是一个重要的未得到满足的需求，给人们带来了巨大的健康和经济问题。 对患者和社会的挑战。疼痛是脊髓损伤患者的常见主诉，其 坚持对他们的生活质量(QOL)有负面影响。大约65%-85%的脊髓损伤患者 这些人中有三分之一的人认为疼痛很严重。虽然一些治疗方法可以减轻严重程度 对于某些个体的疼痛，目前还没有可以持续缓解脊髓损伤疼痛的治疗方法 慢性疼痛人群。持续性疼痛是脊髓损伤的后果之一，一直被证明 显著降低生活质量(QOL)。疼痛会干扰睡眠、认知、情绪和 身体健康和功能正常。疼痛缓解已被确定为未满足需求的最高领域之一 最近对1000名脊髓损伤患者的研究。硬膜外电刺激(EES)，也称为脊髓 刺激疗法(SCS)，是FDA批准的治疗躯干和四肢慢性神经病理性疼痛的常用疗法。 最近的研究表明，EES在脊髓损伤康复中具有促进运动恢复的能力。EES的 病变远端的脊髓成分显示出先前未开发的康复潜力 “完整的”SCI。我们提出了一项双盲、前瞻性、随机的临床试验， 亚急性、创伤性、完全性胸部SCI与美国脊髓损伤协会(亚洲)损害分级 A随机接受疼痛靶区的“EES ON”(治疗)或“EES OFF”(控制) 控制(铅覆盖在脊髓解剖上，与其疼痛分布相对应)和神经恢复 (脊髓圆锥上的铅)作为物理治疗(PT)的辅助。这项研究的目的是 探讨EES改善脊髓损伤患者疼痛和康复效果的可行性。我们 假设接受EES的患者在疼痛和疼痛方面的表现将优于控制组的患者 探索性终点包括运动、感觉、膀胱和生活质量结果。我们还假设，当 控制组跨越到晚期刺激，他们将表现出比早期更小的改善幅度 干预组，但这些患者与他们自己的对照组相比也会有显著的改善 句号。我们提出了以下目标：目标1将比较EES对患者疼痛和生活质量的影响 对照组和安慰剂组之间的SCI，使用多维疼痛问卷的SCI版本 (MPI-SCI)；Aim 2将比较干预前后肌电和测功评估的运动恢复情况 和对照组，最多9个月，然后进行第二次非盲目早期和晚期比较 再刺激9个月；目标3将比较EES对感觉、膀胱和质量的影响- 干预组与对照组间脊髓损伤患者的生活质量、预后。影响：如果成功，这将是 Hear项目将有助于确定这一成熟的临床干预措施是否可以帮助患者 脊髓损伤为神经病理性疼痛，具有较广泛的临床适用性。

ABSTRACT Spinal Cord Injury (SCI) represents a significant unmet need, posing a tremendous health and economic challenge for patients and society. Pain is a common complaint among people affected by SCI, and its persistence negatively impacts their quality of life (QOL). Approximately 65–85% of patients with SCI suffer from pain, and one-third of these characterize the pain as severe. While some treatments reduce the severity of pain in some individuals, no treatments that are currently available consistently relieve pain in the SCI chronic pain population. Persistent pain is one of the consequences of SCI that has consistently been shown to significantly decrease perceived quality of life (QOL). Pain interferes with sleep, cognitive, emotional, and physical health and functioning. Pain relief has been identified as one of the highest areas of unmet needs in a recent study of 1,000 individuals with SCI. Epidural Electrical Stimulation (EES), also known as Spinal Cord Stimulation in (SCS), is a common FDA-approved therapy for chronic neuropathic pain of trunk and limb. Recent studies have demonstrated the ability of EES to augment motor recovery in SCI rehabilitation. EES of spinal elements distal to a lesion has demonstrated previously untapped rehabilitative potential in patients with ‘complete’ SCIs. We propose a double-blind, prospective, randomized clinical trial where patients with subacute, traumatic, complete thoracic SCIs with American Spinal Injury Association (ASIA) Impairment Scale A are randomized to receive either “EES on” (treatment) or “EES off” (control) of the target regions for pain control (lead overlying the spinal cord anatomy corresponding with their pain distribution) and neurorestoration (lead overlying the conus medullaris) as an adjunct to physical therapy (PT). The objective of this study is to examine the feasibility of EES on improving pain and rehabilitation outcomes in patients with SCI. We hypothesize that patients who receive EES will outperform their counterparts in the control group in pain and exploratory endpoints including motor, sensory, bladder and QOL outcomes. We also hypothesize that when the control group crosses over to late stimulation, they will show improvement on a lesser scale than the early intervention group, but that these patients will also show significant improvement compared to their own control period. We propose the following Aims: Aim 1 will compare the impact of EES on pain and QOL in patients with SCI between control and placebo groups, using the SCI version of the Multidimensional Pain Inventory (MPI-SCI); Aim 2 will compare motor recovery as assessed by EMG and dynamometry between intervention and control groups at up to 9-months, followed by a second comparison of unblinded early versus late stimulation for another 9-month period; Aim 3 will compare the impact of EES on sensory, bladder and quality- of-life in patients with SCI between intervention and control groups, outcomes. Impact: If successful, this HEAL project would help determine whether this well-established clinical intervention can help patients with SCI neuropathic pain and have more widespread clinical applicability.