Optimizing functional outcome endpoints for stroke recovery studies

Abstract

Novel therapeutic intervention that aims to enhance the endogenous recovery potential of the brain during the subacute phase of stroke has produced promising results. The paradigm shift in treatment approaches presents new challenges to preclinical and clinical researchers alike, especially in the functional endpoints domain. Shortcomings of the "neuroprotection" era of stroke research are yet to be fully addressed. Proportional recovery observed in clinics, and potentially in animal models, requires a thorough reevaluation of the methods used to assess recovery. To this end, this review aims to give a detailed evaluation of functional outcome measures used in clinics and preclinical studies. Impairments observed in clinics and animal models will be discussed from a functional testing perspective. Approaches needed to bridge the gap between clinical and preclinical research, along with potential means to measure the moving target recovery, will be discussed. Concepts such as true recovery of function and compensation and methods that are suitable for distinguishing the two are examined. Often-neglected outcomes of stroke, such as emotional disturbances, are discussed to draw attention to the need for further research in this area.

Keywords: Behavior; functional outcome; proportional recovery rule; recovery; stroke.

Figure 1.

Fugl-Meyer scores of fitter and non-fitter patients at admission and three months. Fitter (blue) patient receives an FMA score of 36 at admission and from the maximum possible recovery score (black dashed line) of 30 recovers 70% (red dashed line) reaching a final score of 57. Non-fitter patient receives 19 at admission but does not recover according to the proportional recovery rule with minimal increase in FMA scores. Fitter and non-fitter patients differ in lesion size, corticospinal tract integrity and motor-evoked potential responses.