Getting Neurorehabilitation Right

TLDR

Animal models reveal a month of heightened plasticity after stroke, yet the optimal timing and intensity of rehabilitation are unclear, and current inpatient therapy offers brief, low‑intensity training that yields modest impairment improvements. The study aims to translate animal model insights into clinical practice by increasing intensity and dosage of treatments within the first month after stroke, combining noninvasive brain stimulation with robotics, and prioritizing mechanistic phase II research. The authors propose a mechanistic approach that integrates high‑intensity, high‑dose therapy, noninvasive brain stimulation paired with robotic assistance, and motor‑learning‑based mechanistic phase II studies. Very early (<5 days) intense training can increase histological damage, whereas late rehabilitation (>30 days) is less effective for outcomes and plasticity changes.

Abstract

Animal models suggest that a month of heightened plasticity occurs in the brain after stroke, accompanied by most of the recovery from impairment. This period of peri-infarct and remote plasticity is associated with changes in excitatory/inhibitory balance and the spatial extent and activation of cortical maps and structural remodeling. The best time for experience and training to improve outcome is unclear. In animal models, very early (&lt;5 days from onset) and intense training may lead to increased histological damage. Conversely, late rehabilitation (&gt;30 days) is much less effective both in terms of outcome and morphological changes associated with plasticity. In clinical practice, rehabilitation after disabling stroke involves a relatively brief period of inpatient therapy that does not come close to matching intensity levels investigated in animal models and includes the training of compensatory strategies that have minimal impact on impairment. Current rehabilitation treatments have a disappointingly modest effect on impairment early or late after stroke. Translation from animal models will require the following: (1) substantial increases in the intensity and dosage of treatments offered in the first month after stroke with an emphasis on impairment; (2) combinational approaches such as noninvasive brain stimulation with robotics, based on current understanding of motor learning and brain plasticity; and (3) research that emphasizes mechanistic phase II studies over premature phase III clinical trials.