AUTHOR=Spagnolo Francesca , Fichera Mario , Chieffo Raffaella , Dalla Costa Gloria , Pisa Marco , Volonté Maria Antonietta , Falautano Monica , Zangen Abraham , Comi Giancarlo , Leocani Letizia 

TITLE=Bilateral Repetitive Transcranial Magnetic Stimulation With the H-Coil in Parkinson's Disease: A Randomized, Sham-Controlled Study

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.584713

DOI=10.3389/fneur.2020.584713

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> Pilot open-label application of high-frequency repetitive transcranial magnetic stimulation (rTMS) with H-coil in Parkinson's Disease (PD) have shown promising results.</p><p><bold>Objective:</bold> To evaluate safety and efficacy of high-frequency rTMS with H-coil in PD in a double-blind, placebo-controlled, randomized study.</p><p><bold>Methods:</bold> Sixty patients with PD were randomized into 3 groups: M1-PFC (real stimulation on primary motor-M1 and pre-frontal cortices-PFC), M1 (real rTMS on M1, sham on PFC), Sham (apparent stimulation). Primary outcome was baseline-normalized percent improvement in UPDRS part III OFF-therapy at the end of treatment (12 rTMS sessions, 4 weeks). Secondary outcomes were improvement in UPDRS part III sub-scores, timed tests, and neuropsychological tests. Statistical analysis compared improvement following real and sham stimulation at the end of the protocol using either a <italic>t</italic>-test or a Mann-Whitney test.</p><p><bold>Results:</bold> All patients tolerated the treatment and concluded the study. One patient from M1-PFC group was excluded from the analysis due to newly discovered uncontrolled diabetes mellitus. No serious adverse effect was recorded. At the end of treatment, patients receiving real rTMS (M1-PFC and M1 combined) showed significantly greater improvement compared to sham in UPDRS part III total score (<italic>p</italic> = 0.007), tremor subscore (<italic>p</italic> = 0.011), and lateralized sub-scores (<italic>p</italic> = 0.042 for the more affected side; <italic>p</italic> = 0.012 for the less affected side). No significant differences have been oserved in safety and efficacy outcomes between the two real rTMS groups. Notably, mild, not-distressing and transient dyskinesias occurred in 3 patients after real rTMS in OFF state.</p><p><bold>Conclusions:</bold> The present findings suggest that high-frequency rTMS with H-coil is a safe and potentially effective procedure and prompt larger studies for validation as add-on treatment in PD.</p>