Post-Stroke Aphasia and rTMS Treatment (PART) Study

描述（由申请人提供）：中风后失语与高死亡率、显著的运动障碍和社会参与的严重限制有关。在过去的十年里，中风治疗小组在限制中风引起的运动障碍方面取得了很大的进展。不幸的是，失语康复的进展并没有经历同样的快速发展。这一建议是基于我们最近完成的初步研究的初步证据，该研究表明，导航兴奋性重复经颅磁刺激（nerTMS）针对受损半球的残余活动，对中风后失语症的恢复有显著的有益效果本研究的主要目的是对慢性失语症患者进行双盲、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能改善中风后的语言功能。研究结果将对中风后失语症患者产生影响，因为一旦研究完成，结果可用，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，提高社会参与度，提高生活质量，从而改变他们的实践模式。为了填补我们在失语症治疗方面的空白，我们提出了一项研究，其具体目的如下：(1)采用随机、双盲、假对照研究设计，确定nerTMS对失语症康复的比较疗效和最佳剂量。受试者（15名/组）将被随机分配到4个治疗组：(a) 3周的nerTMS， (b) 1周的ST + 2周的nerTMS， (c) 2周的ST +1周的nerTMS，或(d) 3周的ST（对照组）。这种设计将允许系统地评估nerTMS的疗效，并将确定其语言恢复的最佳剂量。短期和长期结果将通过失语测试（AT）和功能磁共振成像（fMRI）进行评估；(2)利用功能磁共振成像（fMRI）评估神经刺激对语言侧化的影响。我们将研究神经tms前语言侧化（fMRI）程度与神经tms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大脑中动脉（LMCA）中风区域的神经tms后的AT表现；(3)探讨约束诱导失语治疗（CIAT）联合nerTMS对20例LMCA脑卒中患者失语恢复的协同作用。这些受试者将接受2周的nerTMS，并辅以每天1小时的CIAT；这两种疗法都将以开放标签的方式进行。患者将接受上述功能磁共振成像和AT评估，并与双盲研究的b组和正在进行的研究（R01 NS048281）中收集的CIAT数据进行比较。这一目的将收集有关神经经颅磁刺激和行为干预可能产生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 impairments 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 which showed 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.1 The main aim of this study is to conduct a double-blind, sham-controlled, dose- response nerTMS treatment trial in subjects with chronic 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 enhanced 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 (15/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. PUBLIC HEALTH RELEVANCE: Loss of language function after stroke (aphasia) is one of the most feared symptoms of stroke because patients lose their ability to interact with society. Language seems to be a fundamentally human cognitive function. Without it, our social and economic status is tremendously impaired. Highly productive members of the society who suddenly lose language capabilities due to a stroke are often devastated and depressed and may not be able to re-enter social and professional life at the pre-stroke level. In this study we will examine the efficacy of (1) navigated excitatory repetitive transcranial magnetic stimulation (nerTMS) and (2) a combination of nerTMS and constraint induced aphasia therapy (CIAT) as post-stroke aphasia rehabilitation methods. We expect that these new types of rehabilitation, either nerTMS alone or in combination with CIAT, will help patients with aphasia return to their lives as they were prior to the stroke.