Sankarasubramanian Vishwanath, Machado Andre G, Conforto Adriana B, Potter-Baker Kelsey A, Cunningham David A, Varnerin Nicole M, Wang Xiaofeng, Sakaie Ken, Plow Ela B
Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Clin Neurophysiol. 2017 Jun;128(6):892-902. doi: 10.1016/j.clinph.2017.03.030. Epub 2017 Mar 21.
The standard approach to brain stimulation in stroke is based on the premise that ipsilesional M1 (iM1) is important for motor function of the paretic upper limb, while contralesional cortices compete with iM1. Therefore, the approach typically advocates facilitating iM1 and/or inhibiting contralesional M1 (cM1). But, this approach fails to elicit much improvement in severely affected patients, who on account of extensive damage to ipsilesional pathways, cannot rely on iM1. These patients are believed to instead rely on the undamaged cortices, especially the contralesional dorsal premotor cortex (cPMd), for support of function of the paretic limb. Here, we tested for the first time whether facilitation of cPMd could improve paretic limb function in severely affected patients, and if a cut-off could be identified to separate responders to cPMd from responders to the standard approach to stimulation.
In a randomized, sham-controlled crossover study, fifteen patients received the standard approach of stimulation involving inhibition of cM1 and a new approach involving facilitation of cPMd using repetitive transcranial magnetic stimulation (rTMS). Patients also received rTMS to control areas. At baseline, impairment [Upper Extremity Fugl-Meyer (UEFM, max=36)] and damage to pathways [fractional anisotropy (FA)] was measured. We measured changes in time to perform proximal paretic limb reaching, and neurophysiology using TMS.
Facilitation of cPMd generated more improvement in severely affected patients, who had experienced greater damage and impairment than a cut-off value of FA (0.5) and UEFM (26-28). The standard approach instead generated more improvement in mildly affected patients. Responders to cPMd showed alleviation of interhemispheric competition imposed on iM1, while responders to the standard approach showed gains in ipsilesional excitability in association with improvement.
A preliminary cut-off level of severity separated responders for standard approach vs. facilitation of cPMd.
Cut-offs identified here could help select candidates for tailored stimulation in future studies so patients in all ranges of severity could potentially achieve maximum benefit in function of the paretic upper limb.
中风患者脑刺激的标准方法基于这样一个前提，即患侧M1（iM1）对瘫痪上肢的运动功能很重要，而健侧皮质与iM1相互竞争。因此，该方法通常主张促进iM1和/或抑制健侧M1（cM1）。但是，这种方法在严重受影响的患者中未能引起太大改善，这些患者由于患侧通路广泛受损，无法依赖iM1。据信这些患者转而依赖未受损的皮质，尤其是健侧背侧运动前区皮质（cPMd）来支持瘫痪肢体的功能。在此，我们首次测试了促进cPMd是否能改善严重受影响患者的瘫痪肢体功能，以及是否能确定一个临界值来区分对cPMd有反应者和对标准刺激方法有反应者。
在一项随机、假刺激对照的交叉研究中，15名患者接受了包括抑制cM1的标准刺激方法和一种使用重复经颅磁刺激（rTMS）促进cPMd的新方法。患者还接受了对对照区域的rTMS。在基线时，测量了损伤程度[上肢Fugl - Meyer评分（UEFM，最大值 = 36）]和通路损伤程度[分数各向异性（FA）]。我们测量了瘫痪上肢近端伸展动作完成时间的变化以及使用TMS测量神经生理学变化。
促进cPMd在严重受影响的患者中产生了更大的改善，这些患者经历的损伤和功能障碍大于FA（0.5）和UEFM（26 - 28）的临界值。相比之下，标准方法在轻度受影响的患者中产生了更大的改善。对cPMd有反应者显示出对iM1施加的半球间竞争得到缓解，而对标准方法有反应者显示患侧兴奋性增加并伴有功能改善。
一个初步的严重程度临界水平区分了对标准方法与促进cPMd有反应者。
此处确定的临界值有助于在未来研究中选择适合个体化刺激的候选者，以便所有严重程度范围内的患者都有可能在上肢瘫痪功能方面获得最大益处。
