Objective: This is a prospective, open-label, single-arm study to assess safety and efficacy of cuneiform(CnF) deep brain stimulation(DBS) in Parkinson’s disease(PD) patients with levodopa-refractory freezing of gait(FOG).

Background: Freezing of gait in Parkinson’s disease (PD) results in substantial disability particularly for those who do not respond to dopaminergic treatments. Our previous work employed, for the first time in humans,  tractography and low frequency directional stimulation to precisely target the cuneiform nucleus (CnF). This study expands our previously published results by presenting the six-month outcomes for four patients with levodopa-resistant FOG who underwent CnF DBS.

Method: This trial enrolled four PD patients with levodopa-resistant FOG (NCT04218526). Bilateral directional DBS leads were implanted into the CnF using pre-operative MRI and diffusion tractography. Electrode placement was performed under light sedation with intraoperative microelectrode recordings. Primary outcomes included the Timed Up and Go (TUG) test, the Pirouette test, and the Freezing of Gait Questionnaire (FOGQ). Quality of life was assessed using the  Quality of Life Questionnaire (PDQL) and the PDQ-39 at six months.

Results: All four patients exhibited significant improvements in freezing of gait. TUG times improved  by 59.4%, from a mean of 66 seconds (±37.8) to 26.4 seconds (±16.8). The Pirouette test showed a 48.95% improvement on the right side and 8.28% on the left, while FOGQ scores improved by 26.58%. However, quality of life assessments (PDQL and PDQ-39) did not reveal improvement in all patients at 28-weeks, likely due to disease progression, increased postural instability and the need for a walker for safe ambulation. MDS-UPDRS improved  21.97% while LEDD decreased 22.60% .

Adverse events included falls and stimulation-related visual side effects which were resolved with appropriate adjustments.

Conclusion: Low frequency directional DBS of the CnF shows promise for managing levodopa-resistant FOG in PD patients. Further research to identify the best neuromodulation parameters for CnF related gait network is necessary to improve outcomes.

References: This Abstract has been submitted for publication to AAN 2025.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/low-frequency-directional-deep-brain-stimulation-of-the-cuneiform-nucleus-for-levodopa-resistant-freezing-of-gait-six-month-outcomes/