Objective: To compare changes in clinical outcomes after weekly low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) sessions over one vs. two pre-motor cortex (preMC) areas in Parkinson’s disease (PD).

Background: The preMC is a key component in the complex system responsible for motor execution. Particularly, dorsal preMC (PMd) and supplementary motor area (SMA) are critically involved in PD pathogenesis due to their broad anatomical and functional connectivity with the basal ganglia and motor cortex (Buhmann et al, 2004; Shirota et al, 2013). Weekly rTMS over SMA has been determined as an effective add-on therapy for PD motor symptoms (Shirota et al, 2013). Nevertheless, the therapeutic potential of combining different premotor targets has never been tested. We designed an active controlled study to explore potential additive effects of rTMS over both SMA and PMd as compared to SMA alone.

Methods: Eighteen PD patients with H&Y scores 2-3 participated in a parallel double-blind randomized study of four weekly sessions of LF rTMS. Outcomes were assessed at baseline and 4 weeks post-treatment completion. Stimulation arms were rTMS over SMA or rTMS over both PMd and SMA (PMd+SMA). Clinical outcomes were total UPDRS-III and axial, tremor, rigidity, and bradykinesia subsets during ON time.

Results: Baseline demographic and clinical characteristics did not differ between groups.

Demographic Characteristics

	SMA-alone (n=6)	PMd+SMA (n=8)	Significance α=0.05
Age	63.17 (6.56)	62.75 (10.14)	n.s.
Sex	4F, 2M	2F, 6M	n.s.
Disease Duration (Years)	7.92 (5.52)	12.70 (6.90)	n.s.
Levodopa Daily Dose	740.83 (504.16)	823.63 (538.94)	n.s.
UPDRS Total	50.17 (9.66)	49.13 (12.24)	n.s.
UPDRS part III	31.67 (5.92)	31.63 (10.39)	n.s.
Hoehn & Yahr	2.33 (0.41)	2.56 (0.42)	n.s.

Table 1” Fourteen patients, 6 SMA-alone and 8 PMd+SMA, completed all study visits. Both interventions, SMA-alone and PMd+SMA, significantly decreased UPDRS-III (z=-2.21, p=0.027; z=-2.53, p=0.011, respectively). Subset analyses showed SMA-alone significantly decreased only bradykinesia subset (z=-2.21, p=0.027) while PMd+SMA decreased both bradykinesia and axial subsets (AxS) (z=-1.98, p=0.048; z=-2.39, p=0.017, respectively). Comparison between arms showed that only PMd+SMA significantly improved AxS (U=5.5, p=0.013). There were no significant differences in changes in total UPDRS-III or any other subset (figure1).

Conclusions: Both rTMS interventions were well-tolerated and improved UPDRS-III total motor scores and bradykinesia. However, improvement in AxS was seen only in the PMd+SMA group, suggesting that LF rTMS over combined preMC areas could be an effective therapy to improve axial symptoms. Larger placebo-controlled studies need to be conducted to corroborate these findings.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/differential-clinical-outcomes-in-unifocal-vs-multifocal-premotor-rtms-for-parkinsons-disease-a-randomized-trial/