Post-Stroke Aphasia and rTMS Treatment (PART) Study

描述(由申请人提供)：中风后的失语症与高死亡率、严重的运动障碍和严重的社会参与限制有关。在过去的十年里，中风小组实施的治疗方法在限制中风引起的运动障碍方面取得了长足的进步。不幸的是，失语症康复方面的进展并没有经历同样迅速的进步。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，针对受影响大脑半球残余活动的导航兴奋性重复经颅磁刺激(NerTMS)对中风后失语的康复具有显著的有益效果。1这项研究的主要目的是在慢性失语症患者中进行一项双盲、假对照、剂量-反应的nerTMS治疗试验。通过进行这项对比试验，我们将提供临床(定性和定量)和成像证据，证明与标准治疗(ST)相比，nerTMS可以改善中风后的语言功能。这一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另一种工具来帮助患者恢复语言技能，从而改善他们的社会参与和生活质量，从而改变他们的实践模式。为了填补我们治疗失语症的空白，我们提出了一项具有以下具体目标的研究：(1)采用随机、双盲、假对照研究设计，确定nerTMS在失语症康复方面的比较疗效和最佳剂量。受试者(15人/组)随机分为4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)。这一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症测试(AT)和功能磁共振成像(FMRI)进行评估；(2)使用功能磁共振成像来评估语言偏侧化的变化。我们将检查神经TMS语言偏侧化程度(FMRI)与NERTMS语言结果(AT)之间的关系，并确定fMRI语言偏侧化是否可以预测针对左侧大脑中动脉(LMCA)卒中区域的NERTMS治疗后的AT表现；(3)探讨强制性失语治疗(CIAT)和nerTMS对20例LMCA卒中患者失语康复的可能协同作用。这些受试者将接受两周的nerTMS治疗，并每天接受1小时的CIAT；两种治疗方法都将以开放标签的方式进行。患者将接受如上所述的功能磁共振成像和AT评估，并与双盲研究中的ARM“b”和正在进行的研究(R01 NS048281)中收集的CIAT数据进行比较。这一目标将收集关于nerTMS和行为干预可能的协同效应的初步数据。 公共卫生相关性：中风后语言功能丧失(失语症)是中风最可怕的症状之一，因为患者失去了与社会互动的能力。语言似乎是人类的一项基本认知功能。没有它，我们的社会和经济地位将受到极大的损害。由于中风而突然丧失语言能力的高生产力社会成员往往会感到崩溃和沮丧，可能无法重新进入中风前的社会和职业生活。在这项研究中，我们将考察(1)导航兴奋性重复经颅磁刺激(NerTMS)和(2)nerTMS与强制性失语治疗(CIAT)相结合作为卒中后失语康复方法的疗效。我们希望这些新型的康复治疗，无论是单独使用NETMS，还是与CIAT结合使用，都将帮助失语症患者恢复中风前的生活。

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.