Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial

• Type of Material: Article
• Authors: Kenneth B. Baker, Cleveland Clinic; Ela B. Plow, Cleveland Clinic; Sean Nagel, Cleveland Clinic; Anson B. Rosenfeldt, Cleveland Clinic; Raghavan Gopalakrishnan, Cleveland Clinic; Cynthia Clark, Cleveland Clinic; Alexandria Wyant, Cleveland Clinic; Madeleine Schroedel, Cleveland Clinic; John Ozinga IV, Cleveland Clinic; Sara Davidson, Cleveland Clinic; Olivia Hogue, Cleveland Clinic; Darlene Floden, Cleveland Clinic; Jacqueline Chen, Cleveland Clinic; Paul J. Ford, Cleveland Clinic; Lauren Sankary, Cleveland Clinic; Xuemei Huang, Cleveland Clinic; David A. Cunningham, Case Western Reserve University; Frank P. DiFilippo, Cleveland Clinic; Bo Hu, Cleveland Clinic; Stephen E. Jones, Cleveland Clinic; Francois Bethoux, Cleveland Clinic; Steven L Wolf, Emory University; John Chae, Case Western Reserve University; André G. Machado, Cleveland Clinic
• Language: English
• Date: 2023-08-14
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1038%2Fs41591-023-02507-0
• Title of Journal or Parent Work: Nature Medicine
• Volume: 29
• Issue: 9
• Start Page: 2366
• End Page: 2374
• Grant/Funding Information: This study was supported by the National Institutes of Health Brain Research Through Advancing Innovative Neurotechnologies Initiative under grant number UH3NS100543 (to A.G.M. and K.B.B.) as well as by Enspire DBS, a spin-off company of Cleveland Clinic.
• Keywords: translational research; medical research; Stroke
• Research Categories: Health Sciences, General; Biology, Neuroscience

Abstract

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In this open-label, non-randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with renewed physical rehabilitation to promote functional reorganization of ipsilesional cortex in 12 individuals with persistent (1–3 years), moderate-to-severe upper-extremity impairment. No serious perioperative or stimulation-related adverse events were encountered, with participants demonstrating a seven-point median improvement on the Upper-Extremity Fugl-Meyer Assessment. All individuals who enrolled with partial preservation of distal motor function exceeded minimal clinically important difference regardless of time since stroke, with a median improvement of 15 Upper-Extremity Fugl-Meyer Assessment points. These robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism. Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery and the need for larger clinical trials. ClinicalTrials.gov registration: NCT02835443.