AUTHOR=Di Lazzaro Vincenzo , Capone Fioravante , Di Pino Giovanni , Pellegrino Giovanni , Florio Lucia , Zollo Loredana , Simonetti Davide , Ranieri Federico , Brunelli Nicoletta , Corbetto Marzia , Miccinilli Sandra , Bravi Marco , Milighetti Stefano , Guglielmelli Eugenio , Sterzi Silvia TITLE=Combining Robotic Training and Non-Invasive Brain Stimulation in Severe Upper Limb-Impaired Chronic Stroke Patients JOURNAL=Frontiers in Neuroscience VOLUME=10 YEAR=2016 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2016.00088 DOI=10.3389/fnins.2016.00088 ISSN=1662-453X ABSTRACT=

Previous studies suggested that both robot-assisted rehabilitation and non-invasive brain stimulation can produce a slight improvement in severe chronic stroke patients. It is still unknown whether their combination can produce synergistic and more consistent improvements. Safety and efficacy of this combination has been assessed within a proof-of-principle, double-blinded, semi-randomized, sham-controlled trial. Inhibitory continuous Theta Burst Stimulation (cTBS) was delivered on the affected hemisphere, in order to improve the response to the following robot-assisted therapy via a homeostatic increase of learning capacity. Twenty severe upper limb-impaired chronic stroke patients were randomized to robot-assisted therapy associated with real or sham cTBS, delivered for 10 working days. Eight real and nine sham patients completed the study. Change in Fugl-Meyer was chosen as primary outcome, while changes in several quantitative indicators of motor performance extracted by the robot as secondary outcomes. The treatment was well-tolerated by the patients and there were no adverse events. All patients achieved a small, but significant, Fugl-Meyer improvement (about 5%). The difference between the real and the sham cTBS groups was not significant. Among several secondary end points, only the Success Rate (percentage of targets reached by the patient) improved more in the real than in the sham cTBS group. This study shows that a short intensive robot-assisted rehabilitation produces a slight improvement in severe upper-limb impaired, even years after the stroke. The association with homeostatic metaplasticity-promoting non-invasive brain stimulation does not augment the clinical gain in patients with severe stroke.