Neuromodulation: Technology at the Neural Interface Received: August 16, 2020 Revised: January 11, 2021 Accepted: January 28, 2021 (onlinelibrary.wiley.com) DOI: 10.1111/ner.13379 How to Identify Responders and Nonresponders to Dorsal Root Ganglion-Stimulation Aimed at Eliciting Motor Responses in Chronic Spinal Cord Injury: Post Hoc Clinical and Neurophysiological Tests in a Case Series of Five Patients Sadaf Soloukey, MSc, MA 1,2 ; Judith Drenthen, MD 3 ; Rutger Osterthun, MD, PhD 4,5 ; Cecile C. de Vos, PhD 6 ; Chris I. De Zeeuw, MD, PhD 2,7 ; Frank J.P.M. Huygen, MD, PhD 6 ; Biswadjiet S. Harhangi, MD, PhD 1 ABSTRACT Objective: While integrity of spinal pathways below injury is generally thought to be an important factor in the success-rate of neuromodulation strategies for spinal cord injury (SCI), it is still unclear how the integrity of these pathways conveying the effects of stimulation should be assessed. In one of our institutional case series of five patients receiving dorsal root ganglion (DRG)-stimulation for elicitation of immediate motor response in motor complete SCI, only two out of five patients presented as responders, showing immediate muscle activation upon DRG-stimulation. The current study focuses on post hoc clinical-neurophysiological tests per- formed within this patient series to illustrate their use for prediction of spinal pathway integrity, and presumably, responder-status. Materials and Methods: In a series of three nonresponders and two responders (all male, American Spinal Injury Association [ASIA] impairment scale [AIS] A/B), a test-battery consisting of questionnaires, clinical measurements, as well as a series of neu- rophysiological measurements was performed less than eight months after participation in the initial study. Results: Nonresponders presented with a complete absence of spasticity and absence of leg reflexes. Additionally, nonre- sponders presented with close to no compound muscle action potentials (CMAPs) or Hofmann(H)-reflexes. In contrast, both responders presented with clear spasticity, elicitable leg reflexes, CMAPs, H-reflexes, and sensory nerve action potentials, although not always consistent for all tested muscles. Conclusions: Post hoc neurophysiological measurements were limited in clearly separating responders from nonresponders. Clinically, complete absence of spasticity-related complaints in the nonresponders was a distinguishing factor between responders and nonresponders in this case series, which mimics prior reports of epidural electrical stimulation, potentially illus- trating similarities in mechanisms of action between the two techniques. However, the problem remains that explicit use and report of preinclusion clinical-neurophysiological measurements is missing in SCI literature. Identifying proper ways to assess these criteria might therefore be unnecessarily difficult, especially for nonestablished neuromodulation techniques. 719 Address correspondence to: Biswadjiet S. Harhangi, MD, PhD, Erasmus MC, Rotterdam Dr. Molenwaterplein 40, 3015 GD (Room Na-2110), Rotterdam, The Nether- lands. Email: b.s.harhangi@erasmusmc.nl 1 Department of Neurosurgery, Erasmus MC, Rotterdam, The Netherlands; 2 Department of Neuroscience, Erasmus MC, Rotterdam, The Netherlands; 3 Department of Clinical Neurophysiology, Erasmus MC, Rotterdam, The Netherlands; 4 Department of Rehabilitation Medicine, Erasmus MC, Rotterdam, The Netherlands; 5 Spinal Cord Injury Department, Rijndam Rehabilitation Center, Rotterdam, The Netherlands; 6 Center for Pain Medicine, Department of Anesthesiology, Erasmus MC, Rotterdam, The Netherlands; and 7 Netherlands Institute for Neuroscience, Royal Dutch Academy for Arts and Sciences (KNAW), Amsterdam, The Netherlands For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http://www. wiley.com/WileyCDA/Section/id-301854.html Source(s) of financial support: The authors have no sources of financial support to report. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Neuromodulation 2021; 24: 719–728 © 2021 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals LLC on behalf of International Neuromodulation Society. www.neuromodulationjournal.com