New York Columbia Collaborative SPOTRIAS

描述（由申请人提供）： 我们最近认为，卒中恢复最好定义为初始损伤的改善过程，而不是恢复终点本身（例如，Fugl-Meyer运动评分（AFM）从基线到卒中后90天的变化）。这一观点有助于调查与恢复有关的生物机制，而不是简单地观察恢复过程的结果。在第一次SPOTRIAS资助中，有三个重要的发现改变了中风恢复研究的前景，并为我们目前提出的研究路线提供了科学基础。第一个发现是比例恢复原则，我们发现所有轻度至中度缺陷的中风患者倾向于恢复其最大潜在恢复的特定比例（-70%），具有高度的可预测性（R= 0.90）。最初描述的是运动功能，同样的原则似乎也适用于语言功能的恢复。第二，在严重的初始损害的患者中，恢复的变异性要大得多--有些患者按比例恢复，有些患者恢复得微不足道。这些非恢复者在临床上与中风后第一周的比例恢复者无法区分，代表了需要进一步表征的一类重要患者;第三项发现满足了最初SPOTRIAS资助的主要具体目标，功能性磁共振成像（fMRI）与在中风发作后平均2天测量获得的脑激活和随后3个月神经损伤的运动恢复程度。这项研究的总体目标是开发一种临床相关的工具，用于预测卒中后最初几天内个体患者的自发恢复，并通过这一过程研究我们假设与AFM重要相关的3个变量的机制作用：初始损伤、皮质脊髓束（CST）上的DWI损伤负荷和fMRI恢复模式的表达。“这一目标将通过以下方式实现：首先通过明确检查康复的影响来验证成比例恢复的原则，然后确定CST的破坏程度与患者的初始损伤和随后的恢复之间的相关性，最后选择最佳预测AFM的模型，单独使用3个变量并结合使用。第二个目标，这将借鉴更多的成像专业知识，从MGH SPOTRIAS网站，是一个重要的指导，以进一步研究干预措施，并将通过测试假设从现存的文献中的必要性和充分性的皮质脊髓束（CST）的途径在恢复。60例急性卒中患者来自哥伦比亚和MGH的卒中服务中心，将采用这种多模式方法进行研究。 相关性：卒中是美国成年人死亡的第三大原因，也是导致残疾的主要原因。更好地了解中风恢复的机制将使我们能够预测谁可能恢复良好，并针对具体的干预措施，以促进恢复过程。

DESCRIPTION (provided by applicant): We have recently argued that stroke recovery is best defined as the process of improvement of the initial impairment rather than as the recovered endpoint itself (for example, change in Fugl-Meyer motor score (AFM) from baseline to 90 days post-stroke). This perspective facilitates the investigation of the biological mechanisms involved with recovery rather than simply looking at the result of the process once it has occurred. In the first SPOTRIAS grant three important discoveries were made that altered the landscape of the investigation of stroke recovery, and which provide the scientific groundwork for our current proposed line of investigation. The first discovery was the principle of proportional recovery, in which we showed that all stroke patients with mild-to-moderate deficits tend to recover a specific proportion (-70%) of their maximum potential recovery with a high degree of predictability (R=.90). Initially described with regard to motor function, the same principle also appears to hold for recovery of language function. Second, in patients with severe initial impairment there is much greater variability in recovery - some follow proportional recovery, and some recover negligibly. These non-recoverers, indistinguishable clinically from proportional recoverers in the first week post-stroke, represent an important class of patient to characterize further; The third discovery, which satisfied the primary specific aim of the original SPOTRIAS grant, was that there is a significant correlation between functional magnetic resonance imaging (fMRI)-measured brain activation acquired at an average 2 days after stroke onset and the degree of motor recovery of the neurological impairment over the subsequent 3 months. The overall goal of this grant is to derive a clinically relevant tool for predicting spontaneous recovery in individual patients within the first few days after stroke, and through this process investigate the mechanistic role of 3 variables that we hypothesize are important correlates of AFM: initial impairment, DWI lesion load on the corticospinal tract (CST), and expression of the fMRI "recovery pattern." This goal will be achieved by first validating the principle of proportional recovery with explicit examination of the influence of rehabilitation, then determining the correlation between degree of disruption of the CST and the patient's initial impairment and subsequent recovery, and finally by selecting the model that best predicts AFM using the 3 variables alone and in combination. The second goal, which will draw on additional imaging expertise from the MGH SPOTRIAS site, is an important guide to further research into interventions, and will be studied by testing hypotheses from the extant literature about the necessity and sufficiency of corticospinal tract (CST) pathways in recovery. Sixty acute stroke patients from the stroke services at Columbia and the MGH will be studied with this multi-modal approach. RELEVANCE: Stroke is the third leading cause of mortality and the leading cause of disability in adults in the US. A better understanding of the mechanisms of stroke recovery will allow us to predict who is likely to recover well and to target specific interventions for development that will enhance the recovery process.