A New Direction for Closed-Loop Spinal Cord Stimulation: Combining Contemporary Therapy Paradigms with Evoked Compound Action Potential Sensing

Abstract

Spinal cord stimulation (SCS) utilizes the delivery of mild electrical pulses via epidural electrodes placed on the dorsal side of the spinal cord, typically to treat chronic pain. The first clinical use of SCS involved the delivery of paresthesia inducing, low-frequency waveforms to the neural targets corresponding to the painful areas. Contemporary SCS therapies now leverage novel therapeutic pathways to limit paresthesia and deliver superior clinical outcomes. Historically, SCS has largely been delivered with fixed stimulation parameters. This approach, referred to as open-loop (OL) SCS, does not account for the fluctuations in spacing—driven by postural changes and activity—between the electrodes and the cord. These fluctuations result in variability in the delivered dose and the volume of tissue activation (VTA) that manifests with each stimulation pulse. Inconsistent dosing may lead to suboptimal therapeutic efficacy and durability. To address this clinical need, closed-loop (CL) SCS systems have been developed to automatically adjust stimulation parameters to compensate for this variability. The evoked compound action potential (ECAP), a biopotential generated by the synchronous activation of dorsal column fibers, is indicative of the VTA resulting from the stimulation pulse. The ECAP may be utilized as a control signal in CL SCS systems to adjust stimulation parameters to reduce variability in the ECAP, and in turn, variability in the VTA. While investigational CL SCS systems with ECAP sensing have so far focused solely on managing paresthesia-based SCS, such systems must also incorporate the stimulation approaches that now define the contemporary clinical practice of SCS. Accordingly, we describe here a flexible, next-generation framework for neural responsive SCS that blends science-based methodologies for pain management with real-time CL control for biophysical variation. We conclude with a clinical example of such a system and the associated performance characteristics.

Spinal Evoked Compound Action Potentials in Rats With Clinically Relevant Stimulation Modalities

“…ECAPs are a clinically valuable tool for quantifying changes in electrophysiologic state, whether as a means to relate perception to a direct measure of neural activation or as feedback signal for controlling the volume of tissue activated with SCS waveforms on a pulse-by-pulse basis. 15,26 And, as first described (albeit in a single animal) by Kent et al, 17 ECAPs may be used to advance understanding of neural activation with both tonic and more modern SCS waveforms in rats, a commonly used preclinical model for SCS research. Our work builds on this concept in several important ways.…”

Machine Learning in Spinal Cord Stimulation for Chronic Pain

“…SCS traditionally delivers stimulation to the dorsal column with fixed parameters including contacts used, amplitude, frequency, and pulse width. 27 This approach is referred to as “open loop” and does not account for the inevitable and persistent physiological changes within the patient and spinal cord. By contrast, closed-loop systems automatically adjust stimulation parameters in response to real-time physiological variables by learning to optimize parameters using control systems and in more advanced systems, ML algorithms.…”

“…[32][33][34][35] More recently, evoked compound action potentials (ECAPs) have demonstrated efficacy as inputs for adaptive SCS. 27,[36][37][38] Pertinently, both these inputs have demonstrated the capacity to be processed by MLbased classifiers. 39,40 Specifically, patients implanted with SCS commonly experience variations in paresthesia perception because of overstimulation or understimulation caused by postural changes.…”

Evoked compound action potentials during spinal cord stimulation: effects of posture and pulse width on signal features and neural activation within the spinal cord

“…That is, the stimulation parameters are fixed unless manually changed. This approach may lead to sub-optimal therapeutic outcomes as the SCS is under-or over-delivered due to frequent movement of the spinal cord relative to the SCS electrodes [7,8].…”