Basics
Introduction
It has been appreciated since Hippocrates that the strongest predictor of final motor impairment after stroke is initial impairment (Aphorisms of Hippocrates, Section 2: 42). A prominent poststroke motor impairment in humans is the intrusion of unwanted synergies, with synergy referring to a systematic pattern of either joint co-articulation or muscle co-activation. The Fugl-Meyer Assessment (FMA) was explicitly developed to track progression of recovery from such synergies. A seminal study tracking the recovery of patients using the upper extremity subscale of the Fugl-Meyer Assessment (FMA-UE) demonstrated that more severely affected patients saw greater recovery in this outcome, on average, than more mildly affected patients in the immediate poststroke recovery period1; however, the average final score of the FMA-UE among the severly affected still trailed behind the mildly affected. The authors of this study stated, “The most dramatic recovery in motor function occurred over the first 30 days, regardless of the initial severity of the stroke.” On the basis of this study and other considerations, Krakauer et al2 sought to investigate the nature of this FMA-UE change early after stroke; work that led to the formulation of the proportional recovery rule (PRR).2 The PRR states that patients recover approximately 70% of their maximal potential reduction in impairment as measured by the FMA.2
Since it was introduced, the PRR has been applied in a broad range of studies that involve recovery from stroke, both for FMA-UE and for other outcomes. Claims related to the PRR have been made for upper and lower limb impairment measured by the FMA,3–10 aphasia measured with the Western Aphasia Battery (WAB),11 the resting motor threshold (RMT) of the extensor carpi radialis,6 and visuospatial neglect measured with the Letter Cancellation Test (LCT),12 among others. Applications of the PRR typically distinguish between two distinct subgroups of patients, referred to as “recoverers” and “nonrecoverers”: the former subgroup is composed of patients who recover a significant amount of lost function, and the latter is composed of those who do not. The PRR is thought to usefully characterize the recovery process among recoverers only. Although the methods by which the PRR was applied and evaluated have differed substantially across publications, many authors have argued that their findings are evidence for a PRR that accurately describes an underlying biological process that arises across neurolocical domains. Recently, however, the PRR has been the subject of criticism related to the validity of the statistical methods underlying its implementation and to the degree to which data are consistent with claims in support of the PRR.13,14 Much of the critique on the PRR articulated by these articles was focused on specific statements associated with the PRR followed by a general dismissal of all findings.
Our goal in this work is to provide a critical reexamination of the literature pertaining to the PRR. We focus first on the interpretation and implementation of PRR as a statistical model, and on data-driven concerns about the use of the PRR in studies of recovery. We then reexamine data reported in the literature and the extent to which past studies provide evidence for the PRR with these considerations in mind. Our hope is that this will serve as an instructive overview of issues that can arise in the application of the PRR to studies of recovery, aiming to improve future investigations into the PRR. Although our primary purpose is not to provide direct response to recent critiques,13,14 we are mindful of the concerns raised and address these directly in the Discussion section.
The breadth of work on the PRR introduces a commensurate range of methodological concerns one might consider. We attempt to be complete in our discussion but prefer to focus on overarching concerns regarding the statistical validity of the PRR instead of point-by-point inspections of the existing literature. Two themes we will revisit while pursuing the main goals of this paper are the identification of recoverers and the distinction between describing biological mechanisms and making patient-level predictions. The manner in which nonrecoverers are identified is a point of legitimate concern, as some statistical approaches can artifactually create evidence for the PRR. The PRR was originally intended to describe biological mechanisms at the population level, although implicitly it is expected that the PRR may be useful for predicting recovery of individual patients. Both of these are related to recent concerns regarding the PRR.
The next section provides an overview of the statistical formulation of the PRR and introduces three simulated datasets to illustrate scenarios over which the PRR shows varying degrees of validity. Subsequent sections conduct a selective review of the literature, reevaluating specific articles in the light of the three scenarios, comment on recent criticisms of the PRR, and end with our current view on the veracity of the PRR.
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TBI Rehabilitation 