Contralaterally Controlled FES Combined with Brain Stimulation for Severe Upper limb Hemiplegia

项目总结/摘要 制定对重度抑郁症患者有效且适当的康复干预措施 上肢轻瘫仍然是主要的未满足的临床需求。这些病人几乎没有意志运动 因此留下了一个没有功能的上肢。许多康复疗法都不适合这一点 因为他们需要大量的剩余运动。我们开发并测试了一种新的 可以在患者中进行的治疗几乎没有残余手/手指运动。称为对侧 受控功能性电刺激（CCFES），该技术应用神经肌肉电刺激 （NMES）至麻痹的腕部、手指和拇指伸肌以产生手张开。患者控制 通过在未受影响的对侧手上戴上带有传感器的手套来测量刺激强度。当 患者张开他们未受影响的手，成比例的刺激强度张开他们麻痹的手。因此，我们认为， 不需要麻痹手的残余运动，这使得即使是患有严重麻痹的患者， 使用受影响的上肢进行功能性任务练习。我们在最近的一项随机对照试验中表明， 在减轻重症患者上肢运动障碍方面比传统NMES更有效。但 患者继续经历功能能力的限制。本研究的目标是在现有成果的基础上， 通过使用另一种技术增强其效果，我们已经证明， 促进这一亚群体的改善。非侵入性脑刺激，以促进 对侧高级运动皮层（cHMC）对严重脑梗死患者的上肢运动控制有积极影响。 患者当病灶同侧皮质脊髓通路的广泛损伤使得受损的病灶同侧皮质脊髓通路 初级运动皮层（iM 1）对控制麻痹肢体运动无效，完整，对侧运动皮层 特别是cHMC可以通过改变运动和运动之间的半球间抑制平衡来发挥作用。 皮层和通过增加从对侧皮层到麻痹患者的非交叉投射的兴奋性 上肢因此，在这里，我们将测试CCFES随着cHMC的促进而增强的科学前提 与CCFES相比， iM 1的常规促进作用或单独的CCFES。72例严重手部损伤患者将 接受12周CCFES + cHMC促进、CCFES + iM 1促进或CCFES +假脑 刺激.上肢运动功能和神经生理学评估将在基线时完成，6， 12、24、36周。本研究将1）确定cHMC易化是否增强CCFES的作用 为了使重症患者的上肢功能得到更大的改善，2）研究潜在的 神经生理机制有助于恢复瘫痪肢体运动控制，和3）评估和识别 影响CCFES + cHMC促进作用疗效的患者因素。 !

PROJECT SUMMARY/ABSTRACT Development of rehabilitation interventions that are both effective and appropriate for patients with severe upper limb paresis remains a major unmet clinical need. These patients have little to no volitional movement and therefore are left with a non-functional upper limb. Many rehabilitation therapies are inappropriate for this sub-population because they require significant residual movement. We have developed and tested a new therapy that can be delivered in patients with little to no residual hand/finger motion. Known as contralaterally controlled functional electrical stimulation (CCFES), the technique applies neuromuscular electrical stimulation (NMES) to paretic wrist, finger, and thumb extensors to produce hand opening. The patient controls the intensity of stimulation by wearing a glove with sensors on their unaffected contralateral hand. When the patient opens their unaffected hand, a proportional intensity of stimulation opens their paretic hand. Therefore, no residual movement of the paretic hand is necessary, which allows even patients with severe paresis to engage in functional task practice using the affected upper limb. We have shown in a recent RCT that CCFES is more effective than conventional NMES at reducing upper limb motor impairment in severe patients. But patients continue to experience limitation in functional abilities. The goal of this study is to build upon the gains achieved with CCFES in severe patients by augmenting its effects with another technique we have shown to facilitate improvements in this sub-population. Non-invasive brain stimulation delivered to facilitate the intact contralesional higher-motor cortices (cHMC) can have positive effects on upper limb motor control in severe patients. When extensive damage to ipsilesional corticospinal pathways renders the damaged ipsilesional primary motor cortex (iM1) ineffective at controlling paretic limb movement, intact, contralesional motor cortices especially the cHMC can contribute by changing the balance of interhemispheric inhibition between motor cortices and by increasing the excitability of uncrossed projections from the contralesional cortex to the paretic upper limb. Therefore, here, we will test the scientific premise that CCFES augmented with facilitation of cHMC will lead to greater upper limb motor improvement in severe patients than CCFES augmented with conventional facilitation of iM1 or than CCFES alone. Seventy-two patients with severe hand impairment will receive 12 weeks of CCFES + cHMC facilitation, CCFES + iM1 facilitation, or CCFES + sham brain stimulation. Assessments of upper limb motor function and neurophysiology will be completed at baseline, 6, 12, 24, and 36 weeks. This study will 1) determine whether cHMC facilitation augments the effects of CCFES to produce greater improvements in upper limb function in severe patients, 2) investigate the underlying neurophysiologic mechanisms contributing to restored paretic limb motor control, and 3) evaluate and identify patient factors that affect efficacy of CCFES + cHMC facilitation. !