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.

Public Health 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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center (P50)
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Special Emphasis Panel (ZNS1-SRB-R (50))
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Janis, Scott
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Columbia University (N.Y.)
Schools of Medicine
New York
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