Measures of Dosage for Spinal-Cord Electrical Stimulation: Review and Proposal

Abstract

This manuscript proposes an electrical definition of therapeutic dose for spinal-cord systems used for the treatment of chronic pain, analogous to the pharmacological definition. Doseresponse relationships are fundamental to pharmacology, radiotherapy, and other treatments, but have never been properly established for neuromodulation. This manuscript offers a robust measure of dose, pre-requisite to establishing a reliable and repeatable dose-response relationship. The new definition, enabled by the system transresistance obtained from measurement of evoked action potentials, recognizes the mechanism of action of spinal cord stimulation (SCS), and should improve acceptance of the therapy as compared to pharmacological treatments which are currently used more frequently for the treatment of chronic pain. The new definition suggests methods for personalization and standardization of the dose in SCS, and is potentially generalizable to all neuromodulation therapies in which nervous tissue is excited including sacral nerve stimulation (SNS), vagal nerve stimulation (VNS) and deep-brain stimulation (DBS). Formulas are provided, and applied using patient data. Powerful conclusions are drawn from application of the new measure.

First evidence of a biomarker-based dose-response relationship in chronic pain using physiological closed-loop spinal cord stimulation

“…measurement allows fair comparison of the amount of activation above threshold across patients and programs, contributing to our ability to observe this relationship. 12 Our finding that pain relief increases with higher dose ratios over threshold suggests a dose-response relationship above and beyond the simple delineation of whether dorsal column activation is occurring. Relationships between dosing levels and patient outcomes may be used to inform a prescriptive level of dose.…”

“…Dose ratio is a standardized metric of dose obtained by taking the ratio of the median ECAP current over the ECAP threshold current and allows for comparisons of dose to be made across patients. 12 The variability metric is defined as the out-of-clinic root mean squared error of the measured dose compared with the target dose. In OL therapy, this error is typically large, as deviations in stimulation delivery from target can occur with even minute physiological movements such as heartbeat and breathing.…”