Lack of progression of beta dynamics after long‐term subthalamic neurostimulation
Objective. To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS). Methods. Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi-pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa™ PC + S, Medtronic, PLC). Resting state STN local field potentials (LFPs) were recorded and motor disability, (the Movement Disorder Society-Unified Parkinson's Disease Rating Scale – motor subscale, MDS-UPDRS III) was assessed off therapy at initial programming, and after 6 months, 1 year, and yearly out to 5 years of treatment. The primary endpoint was measured at 3 years. At each visit, medication had been held for over 12/24 h and DBS was turned off for at least 60 min, by which time LFP spectra reached a steady state. Results. After 3 years of chronic DBS, there were no increases in STN beta band dynamics (p = 0.98) but there were increases in alpha band dynamics (p = 0.0027, 25 STNs). Similar results were observed in a smaller cohort out to 5 years. There was no increase in the MDS-UPDRS III score. Interpretation. These findings provide evidence that the beta oscillopathy does not substantially progress following combined STN DBS plus medication in moderate to advanced Parkinson's disease.
© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Received: 22 August 2021; Accepted: 15 September 2021. This work was supported in part by grant number PF-FBS-1899 and PF-FBS-2024 from the Parkinson's Foundation. Additional funding was provided by the NIH Brain Initiative 1UH3NS107709, NINDS Grant 5 R21 NS096398-02, Michael J. Fox Foundation (9605), NIH Grant AA023165-01A1, Robert and Ruth Halperin Foundation, The Sanches Family Foundation, John A. Blume Foundation and the Helen M. Cahill Award for Research in Parkinson's Disease and Medtronic PLC provided devices but no financial support. The authors would like to thank the members of the Human Motor Control and Neuromodulation Lab and most importantly the participants in the study who without their help, none of this would be possible. Author Contributions. RWA, KBW, MHT, MMK, ZB, EJQ, and HBS contributed to the conception and design of the study; RWA, KBW, JEP, MNP, YK, RSN, DC, MHT, MMK, AV, ZB, EJQ, JH, and HBS contributed to the acquisition and analysis of data; RWA, KBW, MNP, and HBS contributed to drafting the text and preparing the figures. Conflict of Interest. Dr. Bronte-Stewart serves on a clinical advisory board for Medtronic PLC which supplied investigative sensing neurostimulators.
Published - acn3.51463.pdf