Post-Stroke Aphasia and rTMS Treatment (PART) Study

描述（由申请人提供）：卒中后失语症与高死亡率、严重运动障碍和严重限制社会参与相关。在过去的十年中，中风治疗团队在限制中风引起的运动障碍方面取得了很大进展。不幸的是，失语症康复的进展并没有经历同样的快速发展。这项提议是基于我们最近完成的试点研究的初步证据，即针对受影响半球的残余活动的导航兴奋性重复经颅磁刺激（nerTMS）对卒中后失语症的恢复具有显着的有益作用。本研究的主要目的是在慢性（卒中后>1年）失语症受试者中进行双盲、假对照、剂量反应的nerTMS治疗试验。通过进行这项比较试验，我们将提供临床（定性和定量）和影像学证据，证明与标准治疗（ST）相比，nerTMS可改善卒中后的语言功能。这些发现将对中风后失语症患者产生影响，因为一旦研究完成并获得结果，康复专家可能能够通过提供额外的工具来帮助患者恢复语言技能，改善社会参与和改善生活质量来改变他们的实践模式。为了填补我们失语症治疗武器库中的差距，我们提出了一项具有以下特定目标的研究：（1）使用随机、双盲、假对照研究设计来确定nerTMS对失语症恢复的比较疗效和最佳剂量。将受试者（20例/组）随机分配至4个治疗组：（a）3周nerTMS，（B）1周ST + 2周nerTMS，（c）2周ST +1周nerTMS，或（d）3周ST（对照组）。该设计将允许系统评估nerTMS的疗效，并确定其用于语言恢复的最佳剂量。短期和长期结果将通过失语症测试（AT）和fMRI进行评估;（2）使用fMRI评估对nerTMS的语言侧化的变化。我们将检查nerTMS前语言侧化（fMRI）程度与nerTMS后语言结果（AT）之间的关系，并确定fMRI语言侧化是否可以预测针对左侧大脑中动脉（LMCA）卒中区域的nerTMS后的AT表现;（3）探讨限制性失语治疗（CIAT）联合nerTMS对20例LMCA卒中患者失语恢复的可能协同作用。这些受试者将接受为期2周的nerTMS，通过每日1小时的CIAT进行增强;两种治疗均将以开放标签方式给药。将使用上述fMRI和AT对患者进行评价，并与双盲研究的“B”组和正在进行的研究（R 01 NS 048281）中收集的CIAT数据进行比较。这一目标将收集有关nerTMS和行为干预可能的协同效应的初步数据。

DESCRIPTION (provided by applicant): Aphasia after stroke is associated with high mortality, significant motor impairment, and severe limitations in social participation. During the past decade, therapies administered by stroke teams have made great strides to limit the motor impairment caused by stroke. Unfortunately, progress in aphasia rehabilitation has not experienced the same rapid advancement. This proposal is based on preliminary evidence from our recently completed pilot study that navigated excitatory repetitive transcranial magnetic stimulation (nerTMS) targeted to residual activity in the affected hemisphere has a significant beneficial effect on post-stroke aphasia recovery. The main aim of this study is to conduct a double-blind, sham-controlled, dose-response nerTMS treatment trial in subjects with chronic (>1 year after stroke) aphasia. By conducting this comparative trial, we will provide clinical (qualitative and quantitative) and imaging evidence that nerTMS improves language function after stroke when compared to standard treatment (ST). The findings will have implications for patients with post-stroke aphasia in that once the study is completed and the results are available, rehabilitation specialists may be able to change their practice pattern by offering an additional tool to aid patients in recovering their language skills with improved participation in society and improved quality of life. To fill the gap in our therapeutic arsenal for aphasia, we propose a study with the following specific aims: (1) to determine the comparative efficacy and optimal dosing of nerTMS on aphasia recovery using a randomized, double-blind, sham-controlled study design. Subjects (20/group) will be randomly assigned to 4 treatment groups: (a) 3 weeks of nerTMS, (b) 1 week of ST + 2 weeks of nerTMS, (c) 2 weeks of ST +1 week of nerTMS, or (d) 3 weeks of ST (control group). This design will allow systematic evaluation of the efficacy of nerTMS and will determine its most optimal dose for language recovery. Short- and long-term outcomes will be evaluated with aphasia testing (AT) and fMRI; (2) to use fMRI to assess changes in language lateralization in response to nerTMS. We will examine the relationship between the degree of pre-nerTMS language lateralization (fMRI) with the post-nerTMS language outcomes (AT) and determine whether fMRI language lateralization can predict AT performance following nerTMS targeted to the left middle cerebral artery (LMCA) stroke areas; (3) to explore the possible synergistic effect of constraint induced aphasia therapy (CIAT) plus nerTMS on aphasia recovery in a group of 20 LMCA stroke patients. These subjects will receive 2 weeks of nerTMS enhanced by 1 hour of daily CIAT; both therapies will be administered in an open-label fashion. Patients will be evaluated with fMRI and AT as above and compared to the arm "b" of the double-blind study and to CIAT data collected in an ongoing study (R01 NS048281). This aim will gather preliminary data regarding the possible synergistic effects of nerTMS and behavioral intervention.