Durable multimodal and holistic response for physiologic closed-loop spinal cord stimulation supported by objective evidence from the EVOKE double-blind randomized controlled trial.

INTRODUCTION: Chronic pain patients may experience impairments in multiple health-related domains. The design and interpretation of clinical trials of chronic pain interventions, however, remains primarily focused on treatment effects on pain intensity. This study investigates a novel, multidimensional holistic treatment response to evoked compound action potential-controlled closed-loop versus open-loop spinal cord stimulation as well as the degree of neural activation that produced that treatment response. METHODS: Outcome data for pain intensity, physical function, health-related quality of life, sleep quality and emotional function were derived from individual patient level data from the EVOKE multicenter, participant, investigator, and outcome assessor-blinded, parallel-arm randomized controlled trial with 24 month follow-up. Evaluation of holistic treatment response considered whether the baseline score was worse than normative values and whether minimal clinical important differences were reached in each of the domains that were impaired at baseline. A cumulative responder score was calculated to reflect the total minimal clinical important differences accumulated across all domains. Objective neurophysiological data, including spinal cord activation were measured. RESULTS: Patients were randomized to closed-loop (n=67) or open-loop (n=67). A greater proportion of patients with closed-loop spinal cord stimulation (49.3% vs 26.9%) were holistic responders at 24-month follow-up, with at least one minimal clinical important difference in all impaired domains (absolute risk difference: 22.4%, 95% CI 6.4% to 38.4%, p=0.012). The cumulative responder score was significantly greater for closed-loop patients at all time points and resulted in the achievement of more than three additional minimal clinical important differences at 24-month follow-up (mean difference 3.4, 95% CI 1.3 to 5.5, p=0.002). Neural activation was three times more accurate in closed-loop spinal cord stimulation (p<0.001 at all time points). CONCLUSION: The results of this study suggest that closed-loop spinal cord stimulation can provide sustained clinically meaningful improvements in multiple domains and provide holistic improvement in the long-term for patients with chronic refractory pain. TRIAL REGISTRATION NUMBER: NCT02924129.

ECAP-controlled closed-loop versus open-loop SCS for the treatment of chronic pain: 36-month results of the EVOKE blinded randomized clinical trial.

INTRODUCTION: The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant. METHODS: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS. Participants with chronic, intractable back and leg pain refractory to conservative therapy were enrolled between January 2017 and February 2018, with follow-up through 36 months. The primary outcome was a reduction of at least 50% in overall back and leg pain. Holistic treatment response, a composite outcome including pain intensity, physical and emotional functioning, sleep, and health-related quality of life, and objective neural activation was also assessed. RESULTS: At 36 months, more CL-SCS than OL-SCS participants reported ≥50% reduction (CL-SCS=77.6%, OL-SCS=49.3%; difference: 28.4%, 95% CI 12.8% to 43.9%, p<0.001) and ≥80% reduction (CL-SCS=49.3%, OL-SCS=31.3%; difference: 17.9, 95% CI 1.6% to 34.2%, p=0.032) in overall back and leg pain intensity. Clinically meaningful improvements from baseline were observed at 36 months in both CL-SCS and OL-SCS groups in all other patient-reported outcomes with greater levels of improvement with CL-SCS. A greater proportion of patients with CL-SCS were holistic treatment responders at 36-month follow-up (44.8% vs 28.4%), with a greater cumulative responder score for CL-SCS patients. Greater neural activation and accuracy were observed with CL-SCS. There were no differences between CL-SCS and OL-SCS groups in adverse events. No explants due to loss of efficacy were observed in the CL-SCS group. CONCLUSION: This long-term evaluation with objective measurement of SCS therapy demonstrated that ECAP-controlled CL-SCS resulted in sustained, durable pain relief and superior holistic treatment response through 36 months. Greater neural activation and increased accuracy of therapy delivery were observed with ECAP-controlled CL-SCS than OL-SCS. TRIAL REGISTRATION NUMBER: NCT02924129.

Holistic Treatment Response: An International Expert Panel Definition and Criteria for a New Paradigm in the Assessment of Clinical Outcomes of Spinal Cord Stimulation.

BACKGROUND: Treatment response to spinal cord stimulation (SCS) is focused on the magnitude of effects on pain intensity. However, chronic pain is a multidimensional condition that may affect individuals in different ways and as such it seems reductionist to evaluate treatment response based solely on a unidimensional measure such as pain intensity. AIM: The aim of this article is to add to a framework started by IMMPACT for assessing the wider health impact of treatment with SCS for people with chronic pain, a "holistic treatment response". DISCUSSION: Several aspects need consideration in the assessment of a holistic treatment response. SCS device data and how it relates to patient outcomes, is essential to improve the understanding of the different types of SCS, improve patient selection, long-term clinical outcomes, and reproducibility of findings. The outcomes to include in the evaluation of a holistic treatment response need to consider clinical relevance for patients and clinicians. Assessment of the holistic response combines two key concepts of patient assessment: (1) patients level of baseline (pre-treatment) unmet need across a range of health domains; (2) demonstration of patient-relevant improvements in these health domains with treatment. The minimal clinical important difference (MCID) is an established approach to reflect changes after a clinical intervention that are meaningful for the patient and can be used to identify treatment response to each individual domain. A holistic treatment response needs to account for MCIDs in all domains of importance for which the patient presents dysfunctional scores pre-treatment. The number of domains included in a holistic treatment response may vary and should be considered on an individual basis. Physiologic confirmation of therapy delivery and utilisation should be included as part of the evaluation of a holistic treatment response and is essential to advance the field of SCS and increase transparency and reproducibility of the findings.

Occipital Nerve Stimulation for the Treatment of Patients With Medically Refractory Occipital Neuralgia: Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline.

BACKGROUND: Occipital neuralgia (ON) is a disorder characterized by sharp, electrical, paroxysmal pain, originating from the occiput and extending along the posterior scalp, in the distribution of the greater, lesser, and/or third occipital nerve. Occipital nerve stimulation (ONS) constitutes a promising therapy for medically refractory ON because it is reversible with minimal side effects and has shown continued efficacy with long-term follow-up. OBJECTIVE: To conduct a systematic literature review and provide treatment recommendations for the use of ONS for the treatment of patients with medically refractory ON. METHODS: A systematic literature search was conducted using the PubMed database and the Cochrane Library to locate articles published between 1966 and April 2014 using MeSH headings and keywords relevant to ONS as a means to treat ON. A second literature search was conducted using the PubMed database and the Cochrane Library to locate articles published between 1966 and June 2014 using MeSH headings and keywords relevant to interventions that predict response to ONS in ON. The strength of evidence of each article that underwent full text review and the resulting strength of recommendation were graded according to the guidelines development methodology of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Guidelines Committee. RESULTS: Nine studies met the criteria for inclusion in this guideline. All articles provided Class III Level evidence. CONCLUSION: Based on the data derived from this systematic literature review, the following Level III recommendation can be made: the use of ONS is a treatment option for patients with medically refractory ON.