Anatomy of a failure: Chronic interventional paired associative stimulation in stroke (CIPASS)

Abstract

Paired associative stimulation (PAS) is a specific non-invasive brain stimulations technique that allows to modulate motor plasticity in both patients and healthy participants. Our goal was to demonstrate a therapeutic interest for PAS with a lasting increase in motor cortex plasticity for extensor wrist (ECR) muscles and an improvement in upper limb function after 5 days of daily stimulation, in subacute post-stroke patients. A total of 24 patients were included in a double-blind, placebo-controlled trial and randomly assigned to one of two groups (PAS or sham). In the PAS condition, patients underwent a 5-day course of electrical peripheral stimulation, combined with magnetic cortical stimulation, which was applied to the ECR muscle in a single daily session at a frequency of 0.1 Hz for 30 min. It was associated with 2 hours of conventional physiotherapy. Variations in the motor evoked potential (MEP) surface area of the ECR muscle and Upper-Extremity Fugl-Meyer Motor Scale scores were analyzed up to Day 12. No significant difference was observed between the two groups on either electrophysiological or motor parameters. However, repetitive PAS sessions did seem to have an influence on patients with low initial cortical excitability. The negative results underlines some methodological considerations: the inappropriate characteristic of post-stroke MEP for assessing motor recovery, the considerable variability in PAS effects between patients and across the sessions, the heterogeneity of post-stroke population. Five days of daily PAS session failed to improve motor functions in post-stroke patients: PAS cannot be recommended as therapeutic adjuvant in post-stroke rehabilitation.