Author(s):
Barbosa, Raquel ; Bastos, Paulo ; Pita Lobo, Patrícia ; Rodrigues, Catarina Correia ; Valadas, Anabela ; Correia Guedes, Leonor ; Mano, Beatriz ; Alberto, Sara ; Paixão, Vitor ; Rosa, Mário Miguel ; Matias, Ricardo ; Martins, Daniel ; Mendonça, Marcelo ; Coelho, Miguel
Date: 2025
Persistent ID: http://hdl.handle.net/10362/184475
Origin: Repositório Institucional da UNL
Subject(s): deep brain stimulation; freezing of gait; gait analysis; inertial measurement units; Parkinson's disease; Neurology; Clinical Neurology
Description
Funding Information: R.B. was supported by Funda\u00E7\u00E3o para a Ci\u00EAncia e Tecnologia (FCT) through a PhD Scholarship (SFRH/BD/143797/2019) and Pr\u00E9mio Jo\u00E3o Lobo Antunes by Santa Casa da Miseric\u00F3rdia de Lisboa. The funders played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript. M.M. was supported by grant EurDyscover\u2013EJPRD19\u2010135, funded by FCT/MCTES through the European Joint Programme on Rare Diseases (EJPRD/0001/2019), by the Michael J. Fox Foundation (MJFF\u2010023180), and by the PsyPal project (grant agreement number 101137378) funded by the European Union's Horizon Research program. The funders played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript. R.M. is a shareholder of a Kinetikos\u2010affiliated company, which owns the cloud\u2010based platform used in this study. Funding Sources and Conflicts of Interest: Publisher Copyright: © 2025 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Background: The long-term efficacy of high-frequency subthalamic nucleus deep brain stimulation (STN-DBS) on freezing of gait (FOG) remains unclear. We aimed to study the mechanism and optimal therapeutic approach to long-term post-surgery FOG. Objective: The aim was to assess the mechanism and optimal therapeutic approach to long-term post-surgery FOG. Methods: Seventeen Parkinson's disease (PD) STN-DBS patients with a FOG score (item 3.11) ≥2 in the MedON/StimON condition were evaluated under 5 experimental conditions, including a low-frequency (60 Hz) condition maintaining the same total energy delivered. In each condition, gait and FOG episodes (#FOG) were assessed using clinical (eg, a 3 × 14-m Stand-Walk-Sit Test) and kinematic data from inertial measurement units (IMU). Results: Compared to MedOFF/StimOFF, #FOG significantly decreased in the MedON/StimON 130-Hz condition. Either stimulation or levodopa (LD) (MedOFF/StimON or MedON/StimOFF) also significantly reduced #FOG and Stand-Walk-Sit Test (SWS) time compared to MedOFF/StimOFF. No significant difference in #FOG episodes or SWS time was found between 130 and 60 Hz, though 60-Hz stimulation had lower axial scores. Individual responses to LD or stimulation varied: (1) 3 patients improved #FOG with LD but worsened with stimulation, whereas 5 exhibited the reverse; (2) in 9 patients, low-frequency stimulation outperformed high-frequency stimulation in reducing #FOG. Gait variability was the strongest kinematic dimension associated with FOG, with severity accurately identified via a neural network trained on sensor data. Conclusion: Post-DBS FOG in the best-functional state is largely therapy resistant, partially improved by stimulation and medication. Individual variability in responses to LD and stimulation underscores the need to determine FOG circuit mechanisms, as treatment remains an unmet clinical need.
