ISC 2026 | RESTORES trial: repetitive peripheral sensory stimulation for post-stroke upper limb recovery

Yes, I was the principal investigator of the RESTORES study. So the manuscript with the results of the study has recently been accepted for publication. So repetitive peripheral sensory stimulation or RPSS is a non-invasive neuromodulation intervention based on evidence that somatosensory input can modulate motor performance. RPSS enhances sensory input by delivering bursts of electrical stimuli to peripheral nerves, so, for instance, the medial nerve. When suprasensory stimulation, that is stimulation above the sensory threshold, is delivered, paresthesias are elicited in the medial nerve territory. In contrast, when subsensory stimulation is delivered, so stimulation below the sensory threshold, paresthesias are not elicited. And previous studies indicated that suprasensory RPSS can improve motor performance in patients in the chronic phase after stroke. Also, there was a suggestion that subsensory RPSS might be more beneficial than suprasensory intensity in the subacute phase. However, head-to-head comparisons between these two stimulation intensities at different stages after stroke had not yet been performed. So in this multicenter randomized proof-of-principle trial coordinated by the Albert Einstein Hospital, we compared suprasensory and subsensory RPSS delivered to the medial nerve in patients with upper limb paresis in the early subacute and chronic phases after stroke. We assessed motor performance before RPSS, after RPSS, and after motor training. We also measured levels of gamma aminobutyric acid, or GABA, a primarily inhibitory neurotransmitter, plus macromolecules. So we’ll call this measure GABA plus in the primary motor cortex. So we made these measurements using magnetic resonance spectroscopy. And the results were very interesting. So the effects of RPSS on motor performance depended both on stimulation intensity and on phase after stroke. So in the chronic phase, motor performance improved after both stimulation intensities. And an unexpected finding was that in the subacute phase, motor performance worsened after suprasensory stimulation, but improved after subsensory stimulation. We also found that GABA plus levels in the primary motor cortex decreased after suprasensory stimulation in the subacute phase, suggesting that inhibitory cortical mechanisms may respond differently to RPSS early after stroke. It is important to emphasize that motor performance improved across all groups after training. So overall, this finding suggests that neuromodulation should not follow a one-size-fits-all approach. So the results of the studies suggest that the neurobiological response to sensory stimulation varies according to time since stroke. So these results are hypothesis-generating and support tailoring stimulation intensity according to stroke phase in future clinical trials.

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