Objective: To investigate the impact of deep transcranial magnetic stimulation (TMS) of the medial prefrontal cortex (mPFC) on freezing of gait (FOG) in Parkinson’s disease (PD).

Background: FOG is common among patients with advanced PD and is often unresponsive to medications. FOG is frequently triggered during task switching (e.g., gait initiation, turns), processes which have been linked to the mPFC.

Methods: Nine PD patients participated in this pilot study. We applied real and sham deep repetitive TMS using an H3 coil at 10 Hz, over the mPFC. Each patient was assessed before and after 4 weeks of intensive stimulation (3 sessions per week) and 4 weeks of maintenance (once a week) of real and sham TMS. The primary outcome was the score on a FOG-provoking test. The secondary outcomes consisted of the UPDRS-III, the freezing of gait questionnaire (FOG-Q) and spatiotemporal gait parameters. All testing were conducted in the “on” state.

Results: Scores on the FOG-provoking test improved significantly (Δ=-4.14±3.98; p=0.027) after the intensive real TMS treatment; the gains persisted after the maintenance treatment (Δ=-6.00±6.66; p=0.046). The UPDRS-III also improved after real-intensive treatment (Δ=-7.86±6.54; p=0.028), however this effect was not maintained. Conversely, scores on the FOG-provoking test and the motor part of the UPDRS were not significantly affected by the sham treatment.

Gait speed variability was reduced from 8.37±3.59% at baseline to 5.25±1.05% after real treatment (p=0.028). Similarly, stride length variability decreased from 7.46±4.35% at baseline to 4.46±1.00% after real treatment (p=0.046); step time variability decreased from 6.20±1.92% to 4.69±1.25% after real treatment (p=0.028) and swing time variability decreased from 8.87±2.88% to 5.99±1.85% (p=0.028). In contrast, no significant differences were found after the sham stimulation, p>0.05.

The FOG-Q scores did not improve. Due to unexpected arm movement and pain during treatment, two patients dropped out and eventually the study was halted.

Conclusions: This study provides initial cause-and-effect evidence of the role of the PFC in FOG in PD using TMS.  Due to the small sample size and subject pain, the findings should be interpreted with caution. Future work and other non-invasive brain stimulation techniques are needed.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/potential-of-non-invasive-brain-stimulation-to-ameliorate-freezing-of-gait-in-parkinsons-disease-a-deep-repetitive-tms-randomized-double-blinded-cross-over-pilot-study/