Objective: To evaluate the long-term effect of 60Hz low frequency stimulation (LFS) of the subthalamic nucleus (STN) on dysphagia, freezing of gait (FOG) and other motor symptoms in Parkinson disease (PD) patients who have FOG at usual 130Hz high frequency stimulation (HFS).

Background: FOG is frequently reported in patients with bilateral STN DBS, in either medication off or both off and on state, which is often difficult to manage and associated with high morbidity and mortality. LFS of 60Hz, compared to HFS, has been reported to improve FOG and other motor symptoms in short-term studies, with inconsistent long-term benefit given heterogeneity in patient cohorts, stimulation frequency and study designs. LFS of 60Hz also has been reported to improve dysphagia in a 6-week study period. It remains unknown whether there is a long-term benefit of LFS of 60Hz on dysphagia, FOG and other motor symptoms in these patients.

Methods: This is a prospective, sequence randomized, crossover, double blind study. PD patients with medication refractory FOG at 130Hz stimulation of STN were randomized to the sequences of 130Hz, 60Hz or DBS off to assess swallowing function (videofluoroscopic evaluation and swallowing questionnaire), FOG severity (stand-walk-sit test and FOG questionnaire) and motor function (UPDRS-III) at initial visit (V1) and follow-up visit (V2, after being on 60Hz stimulation for an average of 14.5 months), in their usual medications on state. The frequency of aspiration events, perceived swallowing difficulty, and FOG severity at 60Hz compared to 130Hz stimulation at V2, and their corresponding changes at V2 compared to V1 at 60Hz were set as primary outcomes, with similar comparisons in UPDRS-III and its sub-scores as secondary outcomes. Changes in measures between other DBS states were also explored using a paired t-test. Bonferroni correction was applied for multiple comparisons. A multi-variant linear regression model was also used to analyze potential carryover effect.

Results: All 11 enrolled participants completed V1 and 10 completed V2. We found the benefits of 60Hz stimulation compared to 130Hz in reducing aspiration frequency, perceived swallowing difficulty, FOG severity, bradykinesia and overall axial and motor symptoms at V1, and persistent benefits on all of them except dysphagia at V2, with overall decreasing efficacy when comparing V2 to V1. No confounding carryover effect by the order of DBS condition was found.

Conclusions: The 60Hz stimulation, when compared to 130Hz, has long-term benefits on reducing FOG, bradykinesia and overall axial and motor symptoms except dysphagia, although the overall benefits decrease with long-term use.

References: Clinical trial registration ClinicalTrials.gov NCT02549859. The study was supported by Michael J Fox Foundation for Parkinson’s Disease (to TX).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/long-term-effect-of-low-frequency-stimulation-of-stn-on-dysphagia-freezing-of-gait-and-other-motor-symptoms-in-pd/