Non-invasive Brain Stimulation Paired with Standard Physical Therapy in Parkinson's Disease: A Pilot Feasibility Trial

Introduction: In Parkinson’s disease (PD), postural imbalance and gait disorders (PIGD) are predictors of decreased quality of life and survival. PIGD often become unresponsive to pharmacological treatments and are commonly associated with cognitive dysfunction. Physical therapy (PT) training and falls prevention education are considered effective treatments; however, improvements are generally short-lived and only partially maintained. In this population, cognitive dysfunction hampering the consolidation of new motor skills (motor learning) is one principal reason. Transcranial magnetic stimulation (TMS) is an emerging tool for neuro-rehabilitation and growing evidence supports its potential to improve motor learning. Prompted by a shared location between our TMS lab and the PT rehabilitation center, we aimed to test whether adjuvant repetitive TMS combined with PT for PIGD is a feasible neuro-rehabilitation paradigm in patients with PD. Methods: Double blind, randomized, sham-controlled, pilot trial to evaluate the feasibility of recruitment, randomization, retention, assessment procedures and implementation of adjuvant TMS paired back-toback with PT in PD patients with PIGD. Result: 41 paired sessions were completed with 100% adherence. All sessions were tolerated. There were no severe adverse events. One subject withdrew consent. Blinding of study was deemed adequate. The average time between PT and TMS administration was 13.9 (SD 7.3) minutes. After completion of the 5th enrolled subject, the study was early terminated due to relocation of the PD center away from the PT facility. Clinical outcome mean values improved at follow up; however, the small sample size prevented further analysis of efficacy. Conclusions: When the TMS device is located in the proximity of a rehabilitation setting, adjuvant TMS appears to be feasible, safe, and well tolerated in PD. The efficacy of this modality of neuro-rehabilitation and its generalizability remain to be determined.