Background and objectives: The effect of deep brain stimulation (DBS) on gait in patients with Parkinson's disease (PD) is variable but prospective, long-term studies-especially including globus pallidus interna (GPi) stimulation-remain sparse. We tested the hypothesis that subthalamic nucleus (STN) and GPi DBS exert acute and chronic effects on gait in patients with PD. Methods: Gait kinematics were collected prospectively on patients with PD with bilateral or unilateral STN or GPi DBS, at baseline before initial DBS activation (n=104), acutely after activation (n=102), and chronically at 1-month (n=75) and 12-months (n=82). Gait speed was the main outcome measure. Kinematic measures of pace, rhythm, and variability and clinical scales were secondary outcome measures. Results: The average gait speed at baseline in levodopa off state was abnormally slow (80.6 cm/s). DBS activation acutely increased gait speed (97.4 cm/s, p < 0.001) which was maintained at 1- (93.0 cm/s, p < 0.001) and 12-month follow up (91.2 cm/s, p < 0.001). Acute changes during initial programming predicted chronic gait outcomes. When DBS targets were analyzed separately, only patients receiving bilateral STN or GPi DBS improved gait speed along with kinematic measures of pace, rhythm, and variability. Preoperative levodopa response of the MDS-UPDRS axial sub-score correlated with gait speed response to DBS while the total score did not. Discussion: Patients who received either bilateral STN or GPi DBS improved gait kinematic in levodopa off state at 1 year so both targets may be considered for treatment of gait dysfunction, unlike unilateral implantations which resulted in no change. Acute effects of STN or GPi DBS on gait speed should be considered when programming patients as they predict chronic outcomes. When determining DBS candidacy, the degree of axial symptom improvement with levodopa should be considered.

The authors have declared no competing interest.

This study was funded by Emory Udall Center pilot grant (NIH/NINDS P50 NS098685) and the American Parkinsons Disease Association.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Emory University Institutional Review Board gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Anonymized data not published within this article will be made available to any qualified investigator by request to the authors.