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The impact of rehabilitation on post-stroke motor recovery and its dependency on the patient's chronicity remain unclear. The field has widely accepted the notion of a proportional recovery rule with a "critical window for recovery" within the first 3-6 mo poststroke. This hypothesis justifies the general cessation of physical therapy at chronic stages. However, the limits of this critical window have, so far, been poorly defined. In this analysis, we address this question, and we further explore the temporal structure of motor recovery using individual patient data from a homogeneous sample of 219 individuals with mild to moderate upper-limb hemiparesis. We observed that improvement in body function and structure was possible even at late chronic stages. A bootstrapping analysis revealed a gradient of enhanced sensitivity to treatment that extended beyond 12 mo poststroke. Clinical guidelines for rehabilitation should be revised in the context of this temporal structure. NEW & NOTEWORTHY Previous studies in humans suggest that there is a 3- to 6-mo "critical window" of heightened neuroplasticity poststroke. We analyze the temporal structure of recovery in patients with hemiparesis and uncover a precise gradient of enhanced sensitivity to treatment that expands far beyond the limits of the so-called critical window. These findings highlight the need for providing therapy to patients at the chronic and late chronic stages.

JTD Keywords: Motor recovery, Neuroplasticity, Neurorehabilitation, Stroke recovery, Virtual reality

Background: Most stroke survivors continue to experience motor impairments even after hospital discharge. Virtual reality-based techniques have shown potential for rehabilitative training of these motor impairments. Here we assess the impact of at-home VR-based motor training on functional motor recovery, corticospinal excitability and cortical reorganization. Objective: The aim of this study was to identify the effects of home-based VR-based motor rehabilitation on (1) cortical reorganization, (2) corticospinal tract, and (3) functional recovery after stroke in comparison to home-based occupational therapy. Methods: We conducted a parallel-group, controlled trial to compare the effectiveness of domiciliary VR-based therapy with occupational therapy in inducing motor recovery of the upper extremities. A total of 35 participants with chronic stroke underwent 3 weeks of home-based treatment. A group of subjects was trained using a VR-based system for motor rehabilitation, while the control group followed a conventional therapy. Motor function was evaluated at baseline, after the intervention, and at 12-weeks follow-up. In a subgroup of subjects, we used Navigated Brain Stimulation (NBS) procedures to measure the effect of the interventions on corticospinal excitability and cortical reorganization. Results: Results from the system?s recordings and clinical evaluation showed significantly greater functional recovery for the experimental group when compared with the control group (1.53, SD 2.4 in Chedoke Arm and Hand Activity Inventory). However, functional improvements did not reach clinical significance. After the therapy, physiological measures obtained from a subgroup of subjects revealed an increased corticospinal excitability for distal muscles driven by the pathological hemisphere, that is, abductor pollicis brevis. We also observed a displacement of the centroid of the cortical map for each tested muscle in the damaged hemisphere, which strongly correlated with improvements in clinical scales. Conclusions: These findings suggest that, in chronic stages, remote delivery of customized VR-based motor training promotes functional gains that are accompanied by neuroplastic changes. Trial Registration: International Standard Randomized Controlled Trial Number NCT02699398 (Archived by ClinicalTrials.gov at https://clinicaltrials.gov/ct2/show/NCT02699398?term=NCT02699398&rank=1)

JTD Keywords: Stroke, Movement disorder, Recovery of function, neuroplasticity, Transcranial magnetic stimulation, Physical therapy, Hemiparesis, Computer applications software