Divergent Effects of Repetitive Peripheral Stimulation in Subacute and Chronic Stroke: Results From the RESTORES Proof-of-Principle Randomized Trial

BackgroundRepetitive peripheral sensory stimulation (RPSS) delivered above the sensory threshold (RPSS_SUPRA) enhances motor performance and learning in the chronic phase after stroke. Here, we compared the effects of RPSS_SUPRA and RPSS delivered at subsensory intensity (RPSS_SUB) on motor function and levels of γ-aminobutyric acid (GABA)+ (GABA plus coedited macromolecules) measured by proton magnetic resonance spectroscopy in the ipsilesional and contralesional primary motor cortex at different stages post-stroke.MethodsIn this multicenter, randomized proof-of-principle clinical trial, 51 participants in the early subacute or chronic phases after stroke were assigned to receive a single session of either RPSS_SUPRA or RPSS_SUB of the median nerve, followed by motor training. Jebsen-Taylor test (JTT) scores were assessed before RPSS, after RPSS, and after training. GABA+ ipsilesional/contralesional ratios (GABA+_{ipsilesional/contralesional}) were calculated. The data were analyzed with generalized estimation equations with the factors INTERVENTION, GROUP, and TIME.ResultsThe percent change in JTT performance was significantly affected by TIME, with greater improvements after training than after RPSS across groups. For absolute JTT scores, there was a significant INTERVENTION × GROUP × TIME interaction. In the subacute phase, JTT performance declined significantly post-RPSS_SUPRA and improved significantly post-RPSS_SUB, whereas in the chronic phase, performance improved significantly following both RPSS_SUB and RPSS_SUPRA (<i>P</i> < .001 for all Bonferroni comparisons). GABA+_{ipsilesional/contralesional ratios} decreased significantly after RPSS_SUPRA in the subacute phase (<i>P</i> = .008) and remained unchanged in the other groups.ConclusionsSubsensory and suprasensory RPSS have distinct effects on motor performance and M1 GABA+ levels in well-recovered individuals in the subacute and chronic phases post-stroke.Trial Registration:NCT03956407 (2019/05/20).