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.

Subcutaneous Stimulation as Add-on Therapy to Spinal Cord Stimulation in Patients With Persistent Spinal Pain Syndrome Significantly Increases the Total Electrical Charge per Second: Aspects on Stimulation Parameters and Energy Requirements of the Implanted Neurostimulators.

OBJECTIVE: In our previous multicenter randomized controlled trial, we demonstrated the clinical effectiveness of peripheral nerve field stimulation (PNFS) as add-on therapy to spinal cord stimulation (SCS) for the treatment of chronic back pain in patients with persistent spinal pain syndrome (PSPS) or failed back surgery syndrome (FBSS). To our knowledge, no previous study has investigated the effect of PNFS as an add-on to SCS on the energy consumption of the implanted neurostimulators. Therefore, in this study, we compared the specific stimulation parameters and energy requirements of a previously unreported group of patients with only SCS with those of a group of patients with SCS and add-on PNFS. We also investigated differences that might explain the need for PNFS in the treatment of chronic low back pain. MATERIALS AND METHODS: We analyzed 75 patients with complete sets of stimulation parameters, with 21 patients in the SCS-only group and 54 patients in the SCS + PNFS group. Outcome measures were average visual analog scale score, SCS parameters (voltage, frequency, and pulse width), SCS charge per second, and total charge per second. We analyzed baseline characteristics and differences between and within groups over time. RESULTS: Both groups had comparable patient characteristics at baseline and showed a significant decrease in back and leg pain. SCS charge per second did not significantly differ between the groups at baseline or at 12 months. The total charge per second was significantly higher in the active SCS + PNFS group than in the SCS-only group at baseline; in the SCS + PNFS group, this persisted for up to 12 months, and the SCS charge per second and total charge per second increased significantly over time. CONCLUSIONS: Our results show that add-on PNFS increases the total charge per second compared with SCS alone, as expected. However, further research is needed because our results do not directly explain why some patients require add-on PNFS to treat low back pain.

Prospective Cohort Analysis of DRG Stimulation for Failed Back Surgery Syndrome Pain Following Lumbar Discectomy.

INTRODUCTION: Surgical lumbar discectomy is a commonly performed routine spinal procedure that is usually undertaken to alleviate lumbar radicular symptoms caused by a herniated intervertebral disc. Surgical lumbar discectomy can also lead to chronic postsurgical leg and/or back pain (failed back surgery syndrome [FBSS]), a condition that can be refractory to conventional medical management. Early clinical results on the use of dorsal root ganglion (DRG) stimulation for FBSS have supported the use of this treatment alternative. METHODS: A multicenter, single-arm, observational cohort study enrolled patients who had chronic pain following surgical lumbar discectomy, had failed conservative treatments, and reported pain intensity of at least 6 out of 10 in the primary region of pain. Data were collected on pain, quality of life, disability, and mood at baseline and through 12 months. RESULTS: Thirteen patients underwent a trial of DRG stimulation; 11 (84.6%; 95% confidence interval = 57.8% to 95.7%) had good outcomes and underwent permanent device placement. Pain was reduced from a score of 8.64 (±0.92) at baseline to 2.40 (±2.38; n = 9) after 12 months of treatment, a 72.05% average reduction (P < 0.001). Similar improvements were observed across the secondary clinical measures, and safety data were in line with published rates. DISCUSSION: These results suggest that DRG stimulation induces pain relief in subjects diagnosed with FBSS. These reductions in pain were also associated with improvements in quality of life and disability. Additional prospective studies are warranted to further investigate this potential application of DRG stimulation, as well as to optimize patient selection, lead placement, and programming strategies.

Long-Term Effect of Peripheral Nerve Field Stimulation as Add-On Therapy to Spinal Cord Stimulation to Treat Low Back Pain in Failed Back Surgery Syndrome Patients: A 12-Month Follow-Up of a Randomized Controlled Study.

OBJECTIVE: Different approaches in neuromodulation have been used to treat chronic low back pain in failed back surgery syndrome (FBSS) patients. We previously randomized 52 FBSS patients to be treated with spinal cord stimulation (SCS) and additional peripheral nerve field stimulation (PNFS) or SCS alone. At three months, we found a significant reduction of back pain in the PNFS-SCS group compared to the SCS group. In the subsequent open phase part of the study, all patients received optimal SCS and PNFS simultaneously. Here, we present the 12-month follow-up data on back and leg pain. MATERIALS AND METHODS: Data regarding back and leg pain, function, quality of life, patient satisfaction, anxiety and depression, and use of medication were collected by analyzing patients' questionnaires at 12 months and compared with data collected at baseline. Data were analyzed using multilevel regression models. RESULTS: A combined group of 50 subjects completed the 12-month follow-up. Back pain, measured on a 100-mm visual analog scale (VAS), significantly decreased over this period by 30.0 mm (95% CI: [-37.7/-22.4]; p < 0.001), while leg pain decreased by 43.7 mm (95% CI: [-51.5/-36.2]; p < 0.001). We observed statistically significant improvement in almost all secondary outcome measurements. CONCLUSIONS: At 12-month follow-up, PNFS in addition to SCS continues to provide a statistically significant and clinically relevant relief of low back pain in FBSS patients in whom SCS alone is effective for relief of leg pain only.