Durability of Clinical and Quality-of-Life Outcomes of Closed-Loop Spinal Cord Stimulation for Chronic Back and Leg Pain

Abstract

IMPORTANCE Chronic pain is debilitating and profoundly affects health-related quality of life. Spinal cord stimulation (SCS) is a well-established therapy for chronic pain; however, SCS has been limited by the inability to directly measure the elicited neural response, precluding confirmation of neural activation and continuous therapy. A novel SCS system measures the evoked compound action potentials (ECAPs) to produce a real-time physiological closed-loop control system. OBJECTIVE To determine whether ECAP-controlled, closed-loop SCS is associated with better outcomes compared with fixed-output, open-loop SCS at 24 months following implant. DESIGN, SETTING, AND PARTICIPANTSThe Evoke study was a double-blind, randomized, controlled, parallel arm clinical trial with 36 months of follow-up. Participants were enrolled from February 2017 to 2018, and the study was conducted at 13 US investigation sites. SCS candidates with chronic, intractable back and leg pain refractory to conservative therapy, who consented, were screened. Key eligibility criteria included overall, back, and leg pain visual analog scale score of 60 mm or more; Oswestry Disability Index score of 41 to 80; stable pain medications; and no previous SCS. Analysis took place from October 2020 to April 2021. INTERVENTIONS ECAP-controlled, closed-loop SCS was compared with fixed-output, open-loop SCS.MAIN OUTCOMES AND MEASURES Reported here are the 24-month outcomes of the trial, which include all randomized patients in the primary and safety analyses. The primary outcome was a reduction of 50% or more in overall back and leg pain assessed at 3 and 12 months (previously published). RESULTSOf 134 randomized patients, 65 (48.5%) were female and the mean (SD) age was 55.2 (10.6) years. At 24 months, significantly more closed-loop than open-loop patients were responders (Ն50% reduction) in overall pain (53 of 67 [79.1%] in the closed-loop group; 36 of 67 [53.7%] in the open-loop group; difference, 25.4% [95% CI, 10.0%-40.8%]; P = .001). There was no difference in safety profiles between groups (difference in rate of study-related adverse events: 6.0 [95% CI, −7.8 to 19.7]). Improvements were also observed in health-related quality of life, physical and emotional functioning, and sleep, in parallel with opioid reduction or elimination. Objective neurophysiological measurements substantiated the clinical outcomes and provided evidence of activation of inhibitory pain mechanisms.CONCLUSIONS AND RELEVANCE ECAP-controlled, closed-loop SCS, which elicited a more consistent neural response, was associated with sustained superior pain relief at 24 months, consistent with the 3-and 12-month outcomes.

Paresthesia during spinal cord stimulation depends on synchrony of dorsal column axon activation

“…1), their mechanisms are probably more similar than widely speculated. If charge (dose) is correlated with analgesia 44 but limited by paresthesia 10 , then applying pulses at higher rate – at the same or even lower amplitude – can avoid paresthesia while maximizing analgesia ( Fig. 6 ).…”

“…Paresthesia is useful for targeting SCS 5 and, until recently, was considered necessary for SCS-mediated pain relief 4,6 . But paresthesia can be uncomfortable at high SCS intensities 7 (especially when perception threshold is decreased by postural changes 8,9 ), thus limiting the strength of SCS and its therapeutic efficacy 10 . Discovery of paresthesia-free (subperception) forms of SCS is therefore clinically significant [11][12][13][14] .…”

Characterization and applications of evoked responses during epidural electrical stimulation

“…Activation of the large-diameter fibers in the dorsal columns is thought to inhibit pain transmission via gating within the dorsal horn (Zhang et al 2014 ; Yang et al 2011 ) however, several studies suggest that additional segmental and supraspinal mechanisms are involved in EES-induced analgesia (Gilbert et al 2022 ). Variations in the effect of EES to control pain can be attributed to multiple factors, such as initial placement or later migration of the electrode contacts, patient position, and the functional state of the neuronal circuitry (Mekhail et al 2022 ; Pahapill et al 2020 ; Dombovy-Johnson et al 2022 ). Although lead migration can be confirmed through clinical imaging, there is currently no clinically available method to detect and flag the possibility of lead migration for EES automatically and continuously which would allow for decreased loss of efficacy.…”

“…Several approaches have been developed to optimize the electrode placement and stimulation parameter selection of EES with the goal of reducing variation in and increasing therapeutic effectiveness of EES. These range from the classical mapping of paresthesia during trial stimulation (Al-Kaisy et al 2022 ) to recently introduced closed-loop control based on motion/position sensors and/or evoked compound action potential (ECAP) sensing following stimulation (Mekhail et al 2022 ). ECAP components in ESR are produced by the synchronous activation of multiple neuronal fibers in the dorsal column of the spinal cord (He et al 2017 ).…”

Characterization and Applications of Evoked Responses During Epidural Electrical Stimulation

“…Activation of the large-diameter fibers in the dorsal columns is thought to inhibit pain transmission via gating within the dorsal horn (Zhang et al, 2014) (Yang et al, 2011) however, several studies suggest that additional segmental and supraspinal mechanisms are involved in EES-induced analgesia (Gilbert et al, 2022). Variations in the effect of EES to control pain can be attributed to multiple factors, such as initial placement or later migration of the electrode contacts, patient position, and the functional state of the neuronal circuitry (Mekhail et al, 2022) (Pahapill et al, 2020) (Dombovy-Johnson et al, 2022a). Although lead migration can be confirmed through clinical imaging, there is currently no clinically available method to detect and flag the possibility of lead migration for EES automatically and continuously which would allow for decreased loss of efficacy.…”