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

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

doi:10.3389/fneur.2020.584713

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

Front Neurol. 2021 Feb 18:11:584713. doi: 10.3389/fneur.2020.584713. eCollection 2020.

Authors

Francesca Spagnolo^{1

2}, Mario Fichera^{1

2}, Raffaella Chieffo¹, Gloria Dalla Costa^{1

2}, Marco Pisa^{1

2}, Maria Antonietta Volonté³, Monica Falautano⁴, Abraham Zangen⁵, Giancarlo Comi^{1

2}, Letizia Leocani^{1

2}

Affiliations

¹ Experimental Neurophysiology Unit, Institute of Experimental Neurology - INSPE, Scientific Institute Hospital San Raffaele, Milan, Italy.
² San Raffaele Vita-Salute University, Milan, Italy.
³ Neurological Department, Hospital San Raffaele, Milan, Italy.
⁴ Neuropsychology and Clinical Psychology Service, Hospital San Raffaele, Milan, Italy.
⁵ Neuroscience Laboratory, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Abstract

Background: Pilot open-label application of high-frequency repetitive transcranial magnetic stimulation (rTMS) with H-coil in Parkinson's Disease (PD) have shown promising results. Objective: To evaluate safety and efficacy of high-frequency rTMS with H-coil in PD in a double-blind, placebo-controlled, randomized study. Methods: 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 t-test or a Mann-Whitney test. Results: 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 (p = 0.007), tremor subscore (p = 0.011), and lateralized sub-scores (p = 0.042 for the more affected side; p = 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. Conclusions: 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.

Keywords: H-coil = hesed coil; motor cortex; movement disorder; non-invasive brain stimulation (NIBS); rTMS (repetitive transcranial magnetic stimulation).