Background: Stroke rehabilitation aims to reduce impairments and promote activity and participation among patients. A major challenge for stroke rehabilitation research is to develop interventions that can reduce patients' neurological impairments. Until now, there has been no breakthrough in this research field. To move stroke rehabilitation forward, we need more knowledge about underlying mechanisms that drive spontaneous (i.e., reactive) neurobiological recovery after stroke and factors that can be used to optimize its prediction early after stroke onset.
Objective: The aim of the present invited review was therefore to elaborate on the time window of reactive neurobiological recovery, the proportional recovery rule and its generalizability to other neurological impairments, as well as to discuss the consequences for designing stroke recovery and rehabilitation trials.
Methods: In this narrative review, we offer suggestions to optimize the research designs of future stroke rehabilitation and recovery trials post stroke, in order to overcome the current prognostic heterogeneity introduced by variations in the potential for reactive neurobiological recovery.
Findings and conclusions: There is an urgent need for high-quality, explanatory trials in the first three months post stroke. These trials should preferably stratify patients based on their initial potential for reactive neurobiological recovery, measure recovery repeatedly at fixed times post stroke, and differentiate in their outcomes between behavioural restitution and compensation of functions.
Keywords: Stroke; prognosis; proportional recovery; rehabilitation; research design; spontaneous neurobiological recovery.