Neurophysiological and Kinematic Predictors of Response in Chronic Stroke

 描述（由申请人提供）： 上肢轻偏瘫对斯托克卒中幸存者的生活质量和日常生活活动的独立性具有深远而持久的负面影响，然而，尽管进行了许多研究，但在目前的临床实践中没有金标准治疗。我们已经开展了一项渐进的研究计划，该计划已经证明了机器人治疗在慢性中风患者中的有效性，然后优化这些患者接受的机器人治疗和相关治疗的类型。但是，慢性组的平均收益是适度的，尽管直觉认为早期干预将是有益的，但几乎没有数据证实这一点。因此，我们建议利用我们的专业知识，对慢性卒中损伤进行机器人辅助训练，以评估预测模型的潜力，这些模型将选择有更好机会获得功能的患者。我们的临床假设是，存在恢复潜力的运动学和生理学生物标志物，包括功能任务和机器人环境中的基线运动能力，以及经颅磁刺激确定的皮质脊髓束有效性的测量。连接性的功能和解剖学测量以及可塑性相关基因型是要测试的次要生物标志物。中风后的时间是另一个有希望的指标，对临床实践有很强的意义。我们还提出了一个次要的机制假说，即适应不良的transshemispheric皮层抑制将被改变的干预。具体目标：创建干预后功能和残疾的预测模型。测量12周机器人辅助治疗的效果，并在卒中后> 6个月过渡到任务训练。创建一个模型，预测干预后Fugl-Meyer的临床意义变化，并测试模型的有效性。通过使用经颅磁刺激研究沉默期和募集曲线，确定我们的混合训练方法对大脑半球间抑制的影响。将招募具有持续时间>6个月的中度至重度手臂功能障碍（基于7至45的Fugl-Meyer评分）并且医学上稳定并且没有会干扰训练的挛缩或其他损伤的患者。96例受试者将被分配到一个研究组，采用多基线方法，以确保测量的稳定性。评估将由不了解预测模型的检查员进行。前四周的培训将包括手腕机器人培训课程，第二四周将包括平面机器人培训课程，第三四周将包括交替手腕和平面培训课程。机器人培训课程将持续45分钟，然后是15分钟的功能相关任务培训（翻译到任务培训（TTT））。临床评价将包括卒中影响量表（主要结局）、Fugl-Meyer上肢运动表现部分测试、Wolf运动功能测试、行动研究手臂测试和家庭手臂使用的活动监测器。运动学分析将在训练前和训练后进行。大多数患者将同意接受TMS和MRI。在这些受试者中，将在每次结局测量访视时确定半球内抑制。仅在基线期进行MRI，并将用于确定皮质脊髓束的病变类型、白色完整性和功能连通性。结束时 这些目标是，我们将有一种关于中风后晚期强化手臂治疗的临床决策方法，以及对其如何工作的更好的机械理解。该方法将在整个VA医疗系统和其他地方传播。

 DESCRIPTION (provided by applicant): Upper extremity hemiparesis has a profound and lasting negative impact on quality of life and independence in activities of daily living for stoke survivors, yet, despite many investigations, there are no gold standard treatments in current clinical practice. We have carried out a progressive research program that has demonstrated the effectiveness of robotic therapy in chronic stroke patients, and then optimizing the type of robotic therapy and associated therapy that these patients receive. But gains in the chronic group are modest on average, and despite an intuition that earlier intervention will be beneficial, there is little data to confirm that. Therefore, we propose to build upon our expertise with robot-assisted training for chronic stroke impairment in order to evaluate the potential of predictive models that would select patients with better chances of making functional gains. Our clinical hypothesis is that kinematic and physiological biomarkers of recovery potential exist, and include baseline motor ability in both functional tasks and in the robotic environment, and measures of corticospinal tract effectiveness determined by transcranial magnetic stimulation. Functional and anatomical measures of connectivity, and plasticity relevant genotype are secondary biomarkers to test. Time after stroke is another promising marker to test, with strong implications for clinical practice. We also propose a secondary mechanistic hypothesis that maladaptive transhemispheric cortical inhibition will be altered by the intervention. Specific Objectives: Create a predictive model of function and disability following the intervention. Measure the effects of 12 weeks of robot-assisted therapy and transition to task training at > 6 months after stroke. Create a model that predicts clinically meaningful change in Fugl-Meyer in response to the intervention and test the validity of the model. Determine the effect our hybrid method of training has on interhemispheric inhibition by using transcranial magnetic stimulation to study silent period and recruitment curve. Patients with moderate to severe arm dysfunction (based on Fugl-Meyer scores of 7 to 45) of >6 months duration who are medically stable and do not have contractures or other impairments that would interfere with training will be enrolled. 96 subjects will be assigned to a single study arm with a multiple baseline approach to ensure stability of measures. Evaluations will be conducted by an examiner who has no knowledge of the predictive model. The first four weeks of training will consist of wrist robot training sessions, te second four weeks will consist of planar robot training sessions and the third four weeks will consist of alternation wrist and planar training sessions. Robot training sessions will be 45 minutes in duration followed by 15 minutes of training on functionally relevant tasks (translation to task training (TTT)). Clinical evaluations will include Stroke Impact Scale (Primary Outcome), Fugl-Meyer Upper Extremity Motor Performance Section Test, Wolf Motor Function Test, Action Research Arm Test, and activity monitor of home arm use. Kinematic analysis will be conducted pre and post training. A majority of patients will be consented for TMS and MRI. In those subjects intrahemispheric inhibition will be determined at each outcomes measurement visit. MRI will be performed only at the baseline period, and will be used to define the lesion type, white matter integrity and functional connectivity of the corticospinal tract. At the conclusion of these aims we will have a method for clinical decision-making regarding intensive arm therapy late after stroke, and a better mechanistic understanding of how it works. The method will be disseminated throughout the VA medical system and beyond.